You searched for subject:(DNA PK).
Showing records 1 – 25 of
25 total matches.
No search limiters apply to these results.
University of Melbourne
1.
AZAD, ARUN.
Targeting DNA-dependent protein kinase promotes accelerated senescence of irradiated human cancer cells.
Degree: 2012, University of Melbourne
URL: http://hdl.handle.net/11343/37954 
► Ionizing radiation is a widely used anti-cancer modality. Unfortunately however, relapse rates are high following radiation treatment indicating an urgent need for novel radiosensitizing strategies.…
(more)
▼ Ionizing radiation is a widely used anti-cancer modality. Unfortunately however, relapse rates are high following radiation treatment indicating an urgent need for novel radiosensitizing strategies. Since radiation potently induces DNA double-strand breaks (DSBs), targeting signaling networks involved in DSB repair is a promising approach for enhancing cellular radiosensitivity. In mammalian cells the primary repair mechanism of radiation-induced DSBs is the non-homologous end-joining (NHEJ) pathway, in which DNA-dependent protein kinase (DNA-PK) plays a critical role. As a result, DNA-PK potentially represents an important molecular target for inhibiting DSB repair and enhancing the cytotoxicity of radiation.
Using BEZ235, a novel small molecule inhibitor of DNA-PK and phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) currently in clinical trials, the first aim of this thesis was to characterize the effects of inhibiting DNA-PK on tumor radiosensitivity in vitro and in vivo. The second aim of this thesis was to examine the mechanisms through which DNA-PK inhibition improves tumor radiosensitivity as little is known about the mechanisms involved in the radiation-enhancing effects of DNA-PK blockade.
BEZ235 was seen to abrogate radiation-induced DSB repair and potently increase the radiosensitivity of H460 and A549 cells, human non-small cell lung cancer (NSCLC) cell lines. BEZ235 also potentiated the anti-tumor activity of ionizing radiation in H460 xenografts. Significantly, radiation enhancement by BEZ235 coincided with a prominent p53-dependent accelerated senescence phenotype characterized by positive β-galactosidase staining, G2-M cell-cycle arrest, enlarged and flattened cellular morphology, increased p21 expression and senescence-associated cytokine secretion.
Subsequent experiments sought to examine the mechanisms involved in the pro-senescence response of irradiated cells to BEZ235, and specifically whether selective inhibition of DNA-PK is sufficient to promote accelerated senescence after radiation. Significantly, it was shown that specific pharmacological inhibition of DNA-PK but not PI3K or mTORC1 delays DSB repair leading to accelerated senescence after radiation. It was additionally demonstrated that PRKDC knock down using small interfering RNA promotes a striking accelerated senescence phenotype in irradiated cells comparable to that of BEZ235.
Collectively, these data establish accelerated senescence as a novel mechanism of radiosensitization induced by DNA-PK blockade and underline the emerging link between unrepaired DSBs and enforcement of p53-dependent accelerated senescence. These data highlight the potential benefits of using DNA-PK blockade to modulate repair of therapeutically-induced DSBs and thereby promote radiation-induced accelerated senescence. In turn, these findings provide a…
Subjects/Keywords: DNA-PK; DNA-PKCs; senescence; radiation; BEZ235; DNA damage
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
AZAD, A. (2012). Targeting DNA-dependent protein kinase promotes accelerated senescence of irradiated human cancer cells. (Doctoral Dissertation). University of Melbourne. Retrieved from http://hdl.handle.net/11343/37954
Chicago Manual of Style (16th Edition):
AZAD, ARUN. “Targeting DNA-dependent protein kinase promotes accelerated senescence of irradiated human cancer cells.” 2012. Doctoral Dissertation, University of Melbourne. Accessed April 17, 2021.
http://hdl.handle.net/11343/37954.
MLA Handbook (7th Edition):
AZAD, ARUN. “Targeting DNA-dependent protein kinase promotes accelerated senescence of irradiated human cancer cells.” 2012. Web. 17 Apr 2021.
Vancouver:
AZAD A. Targeting DNA-dependent protein kinase promotes accelerated senescence of irradiated human cancer cells. [Internet] [Doctoral dissertation]. University of Melbourne; 2012. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/11343/37954.
Council of Science Editors:
AZAD A. Targeting DNA-dependent protein kinase promotes accelerated senescence of irradiated human cancer cells. [Doctoral Dissertation]. University of Melbourne; 2012. Available from: http://hdl.handle.net/11343/37954
Vanderbilt University
2.
Nam, Edward Adam.
Phospho-regulation of the DNA Damage Response Kinase ATR.
Degree: PhD, Cancer Biology, 2011, Vanderbilt University
URL: http://hdl.handle.net/1803/14069
► Understanding how cells maintain genome integrity is necessary to gain insight into the pathology of cancer and to identify therapeutic targets and biomarkers. The DNA…
(more)
▼ Understanding how cells maintain genome integrity is necessary to gain insight into the pathology of cancer and to identify therapeutic targets and biomarkers. The
DNA damage response kinase ATR is essential for the maintenance of the cellular genome. In this dissertation, I hypothesize that ATR is phosphorylated in response to
DNA damage. I also characterize a novel ATR inhibitor and explore its efficacy as an anti-cancer agent. I discover that ATR is phosphorylated on T1989 in response to
DNA damage and marks an activated kinase. T1989 phosphorylation is not critical for ATR function. As a proximal marker for ATR activity, T1989 phosphorylation has significant potential as a biomarker. I also identify a novel regulatory region in ATR that separates the essential function of ATR from its G2 checkpoint activity. Finally, I demonstrate that an ATR inhibitor sensitizes cells to replication stress, suggesting ATR inhibition may be a good therapeutic strategy to pursue.
Advisors/Committee Members: Ellen Fanning (committee member), Sandra Zinkel (committee member), David Cortez (committee member), Graham Carpenter (committee member), Albert Reynolds (Committee Chair).
Subjects/Keywords: replication stress; DNA-PK; ATR; ATM; DNA damage
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Nam, E. A. (2011). Phospho-regulation of the DNA Damage Response Kinase ATR. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/14069
Chicago Manual of Style (16th Edition):
Nam, Edward Adam. “Phospho-regulation of the DNA Damage Response Kinase ATR.” 2011. Doctoral Dissertation, Vanderbilt University. Accessed April 17, 2021.
http://hdl.handle.net/1803/14069.
MLA Handbook (7th Edition):
Nam, Edward Adam. “Phospho-regulation of the DNA Damage Response Kinase ATR.” 2011. Web. 17 Apr 2021.
Vancouver:
Nam EA. Phospho-regulation of the DNA Damage Response Kinase ATR. [Internet] [Doctoral dissertation]. Vanderbilt University; 2011. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/1803/14069.
Council of Science Editors:
Nam EA. Phospho-regulation of the DNA Damage Response Kinase ATR. [Doctoral Dissertation]. Vanderbilt University; 2011. Available from: http://hdl.handle.net/1803/14069
University of Edinburgh
3.
Parker, James M.
Structural studies of two proteins involved in the maintenance of genomic stability, FEN 1 and DNA-PKcs.
Degree: PhD, 2016, University of Edinburgh
URL: http://hdl.handle.net/1842/21709
► Genomic stability refers to an organism’s ability to maintain and pass forward its genetic information. There are a raft of proteins and pathways whose sole…
(more)
▼ Genomic stability refers to an organism’s ability to maintain and pass forward its genetic information. There are a raft of proteins and pathways whose sole purpose is maintaining this stability through swiftly replicating DNA as well as accurately repairing damage caused through contact with endogenous and exogenous DNA damaging elements. This study will focus on the structural aspects of two proteins that play a part in different areas of genome maintenance. Flap Endonuclease 1 (FEN 1) works in DNA replication, where it is tasked with removing a small RNA flap that is created during Okazaki fragment formation. This flap removal is essential to mature these fragments into one continuous strand of nascent DNA. Using the archeon Pyrococcus abyssi (Pab) as a model system has the advantage of possessing simple replicative machinery, whilst bearing striking similarities with the human system. Pab is a hyperthermophilic, piezophile meaning it thrives in conditions of high temperature and pressure. DNA-dependent protein kinase (DNA-PK) is a holoenzyme that plays a role in the Non Homologous End Joining (NHEJ) pathway by repairing DNA double strand breaks (DSB’s). In cancer therapy, a patient is exposed to DNA damaging elements, leading to an ever-increasing population of DSBs. If an inhibitor of DNA-PKcs were introduced along with this therapy it could potentiate its effect, as the cancerous cells will be less able to repair the damage. The aim of this part of the study is to determine a protocol to generate pure, soluble, correctly folded protein for the purposes of biophysical characterisation and X-ray crystallographic structural studies.
Subjects/Keywords: 572.8; cellular repair pathways; DNA-PK; FEN 1; genome maintenance; protein
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Parker, J. M. (2016). Structural studies of two proteins involved in the maintenance of genomic stability, FEN 1 and DNA-PKcs. (Doctoral Dissertation). University of Edinburgh. Retrieved from http://hdl.handle.net/1842/21709
Chicago Manual of Style (16th Edition):
Parker, James M. “Structural studies of two proteins involved in the maintenance of genomic stability, FEN 1 and DNA-PKcs.” 2016. Doctoral Dissertation, University of Edinburgh. Accessed April 17, 2021.
http://hdl.handle.net/1842/21709.
MLA Handbook (7th Edition):
Parker, James M. “Structural studies of two proteins involved in the maintenance of genomic stability, FEN 1 and DNA-PKcs.” 2016. Web. 17 Apr 2021.
Vancouver:
Parker JM. Structural studies of two proteins involved in the maintenance of genomic stability, FEN 1 and DNA-PKcs. [Internet] [Doctoral dissertation]. University of Edinburgh; 2016. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/1842/21709.
Council of Science Editors:
Parker JM. Structural studies of two proteins involved in the maintenance of genomic stability, FEN 1 and DNA-PKcs. [Doctoral Dissertation]. University of Edinburgh; 2016. Available from: http://hdl.handle.net/1842/21709
Université Paris-Sud – Paris XI
4.
Kotula, Ewa.
The role of DNA-dependent protein kinase in tumor metastasis : Le rôle de la protéine kinase dépendante de l’ADN (DNA-PK) dans le processus métastatique.
Degree: Docteur es, Cancérologie / Radiobiologie, 2014, Université Paris-Sud – Paris XI
URL: http://www.theses.fr/2014PA11T021
► La protéine kinase dépendante de l’ADN (DNA-PK) est une sérine-thréonine kinase qui est un élément essentiel dans la voie de réparation de l’ADN endommagé par…
(more)
▼ La protéine kinase dépendante de l’ADN (DNA-PK) est une sérine-thréonine kinase qui est un élément essentiel dans la voie de réparation de l’ADN endommagé par recombinaison non-homologue (non-homologous end-joining; NHEJ). DNA-PK est également impliquée dans de nombreux processus cellulaires autre que la réparation de l'ADN. Plusieurs travaux ont montré que les protéines impliquées dans la réparation des dommages de l'ADN tels que BRCA-1, MRN-11, PARP-1 et également de DNA-PK jouent un rôle important dans la métastase du cancer. Dans ce travail, nous nous sommes concentrées sur le rôle de DNA-PK dans les métastases du mélanome. Dans un premier temps, en utilisant les molécules Dbait 32Hc comme un moyen d'activer DNA-PK dans le noyau et le cytoplasme, nous avons identifié plusieurs nouvelles cibles cytoplasmiques de DNA-PK, dont la vimentine. Nous avons montré que DNA-PK phosphoryle la vimentine sur Ser459 et que cette forme phosphorylée est la plupart du temps située au niveau des protrusion cellulaires des cellules migratrices. Nous avons ensuite démontré que la vimentine-Ser459-P induite par le traitement de Dbait32Hc participe à l'inhibition de l'adhésion et la migration cellulaire. Ainsi, cette approche a conduit à l'identification de nouvelles cibles cytoplasmiques de DNA-PK et a révélé un lien entre la signalisation des dommages de l'ADN et le cytosquelette. Ensuite, nous avons montré que DNA-PK joue un rôle important dans la migration et invasion cellules en régulant la sécrétion des facteurs associés à la métastase. Nous avons montré que l'absence ou l’inhibition de DNA-PK conduit à une régulation négative des facteurs pro-métastatique sécrétés et à la régulation positive de facteurs anti-métastatiques sécrétés tels que les inhibiteurs des métalloprotéinases matricielles. Nous avons confirmé le rôle de DNA-PK in vivo dans l'implantation de la tumeur primaire et dans la formation des métastases. Ainsi, nos études ont évalué le rôle de DNA-PK sur le contrôle du microenvironnement de la tumeur par le contrôle de la sécrétion de facteurs importants pour la métastase. En résumé, nos résultats mettent en évidence l'importance de la DNA-PK comme cible de traitement anti-métastatique.
The DNA-dependent protein kinase (DNA-PK) is a serine/threonine protein kinase, which is a critical component of the DNA-damage repair pathways through non-homologous end-joining (NHEJ). Besides DNA repair, it is also involved in numerous cellular pathways. Emerging results show that proteins involved in DNA damage repair such as BRCA-1, MRN-11, PARP-1 and also DNA-PK could play a role in cancer metastasis. In the current study, we demonstrated the role of DNA-PK in melanoma metastasis. Firstly using Dbait 32Hc molecules as a tool for specifically activating DNA-PK in a nucleus and cytoplasm, we identified several new cytoplasmic targets of DNA-PK including vimentin. We established that DNA-PK phosphorylates vimentin on Ser459 and that this phosphorylation was mostly located at cell protrusions of melanoma migratory cells. Following…
Advisors/Committee Members: Dutreix, Marie (thesis director).
Subjects/Keywords: DNA-PK; Réparation d’ADN; Dbait; Vimentine; Métastase; La migration; L’invasion; La sécrétion; DNA-PK; DNA repair; Dbait; Vimentin; Metastasis; Migration; Invasion; Secretion
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Kotula, E. (2014). The role of DNA-dependent protein kinase in tumor metastasis : Le rôle de la protéine kinase dépendante de l’ADN (DNA-PK) dans le processus métastatique. (Doctoral Dissertation). Université Paris-Sud – Paris XI. Retrieved from http://www.theses.fr/2014PA11T021
Chicago Manual of Style (16th Edition):
Kotula, Ewa. “The role of DNA-dependent protein kinase in tumor metastasis : Le rôle de la protéine kinase dépendante de l’ADN (DNA-PK) dans le processus métastatique.” 2014. Doctoral Dissertation, Université Paris-Sud – Paris XI. Accessed April 17, 2021.
http://www.theses.fr/2014PA11T021.
MLA Handbook (7th Edition):
Kotula, Ewa. “The role of DNA-dependent protein kinase in tumor metastasis : Le rôle de la protéine kinase dépendante de l’ADN (DNA-PK) dans le processus métastatique.” 2014. Web. 17 Apr 2021.
Vancouver:
Kotula E. The role of DNA-dependent protein kinase in tumor metastasis : Le rôle de la protéine kinase dépendante de l’ADN (DNA-PK) dans le processus métastatique. [Internet] [Doctoral dissertation]. Université Paris-Sud – Paris XI; 2014. [cited 2021 Apr 17].
Available from: http://www.theses.fr/2014PA11T021.
Council of Science Editors:
Kotula E. The role of DNA-dependent protein kinase in tumor metastasis : Le rôle de la protéine kinase dépendante de l’ADN (DNA-PK) dans le processus métastatique. [Doctoral Dissertation]. Université Paris-Sud – Paris XI; 2014. Available from: http://www.theses.fr/2014PA11T021
5.
Cristini, Agnese.
DNA double-strand break formation and signalling in response to transcription-blocking topoisomerase I complexes : Formation et signalisation des cassures double-brin de l'ADN lors d'un blocage de la transcription.
Degree: Docteur es, Biotechnologies, cancérologie, 2015, Université Toulouse III – Paul Sabatier
URL: http://www.theses.fr/2015TOU30276
► La topoisomérase I (Top1) élimine les surenroulements de l'ADN générés lors de la transcription en produisant transitoirement des complexes de clivage Top1-ADN (Top1cc). Ces Top1cc…
(more)
▼ La topoisomérase I (Top1) élimine les surenroulements de l'ADN générés lors de la transcription en produisant transitoirement des complexes de clivage Top1-ADN (Top1cc). Ces Top1cc transitoires peuvent être stabilisés par les camptothécines, dont sont dérivés des agents anticancéreux, et par les fréquentes altérations de l'ADN. Bien que les Top1cc stabilisés soient des lésions qui bloquent efficacement la transcription, la compréhension des processus moléculaires qui résultent du blocage des complexes transcriptionnels par les Top1cc est encore limitée. Des travaux précédents ont montré que les Top1cc stabilisés produisent des cassures double-brin (DSBs) de l'ADN dépendantes de la transcription qui activent ATM. Dans ce projet, nous avons utilisé des cellules quiescentes traitées avec la camptothécine pour induire des Top1cc bloquant la transcription et nous avons étudié les mécanismes de la production et de la signalisation des DSBs. Nous montrons que les DSBs sont produites préférentiellement dans les régions sub-télomériques lors de la réparation des Top1cc bloquant la transcription par les cassures simple-brin de l'ADN générées après la protéolyse de la Top1 et avant l'action de Tdp1. L'analyse de la signalisation de ces DSBs révèle une nouvelle fonction de DNA-PK dans la promotion de l'ubiquitinylation conduisant (i) à l'activité complète d'ATM aux sites des DSBs en favorisant l'ubiquitination d'H2AX et H2A, et (ii) à l'augmentation de la réparation des Top1cc en favorisant la protéolyse de la Top1. Enfin, nous montrons que les DSBs co-transcriptionnelles induisent la mort des cellules quiescentes. L'ensemble de ces résultats apportent un nouvel aperçu des réponses cellulaires aux camptothécines, et suggèrent que les DSBs qui résultent des Top1cc bloquant la transcription puissent contribuer à la pathogénèse du syndrome neurodégénératif SCAN1, qui est causé par une déficience en Tdp1.
Topoisomerase I (Top1) removes DNA supercoiling generated during transcription by producing Top1-DNA cleavage complexes (Top1cc). These transient Top1cc can be stabilized by camptothecins, from which anticancer drugs are derived, and by common DNA alterations. Although stabilized Top1cc are potent transcription-blocking lesions, our understanding regarding the molecular processes resulting from the stalling of transcription complexes by Top1cc is currently limited. Previous work showed that stabilized Top1cc produce transcription-dependent DNA double-strand breaks (DSBs) that activate ATM signalling. In this project, we used camptothecin-treated quiescent cells to induce transcription-blocking Top1cc and study the mechanisms of DSB production and signalling. We show that DSBs form preferentially at subtelomeric regions during the repair of transcription-blocking Top1cc from DNA single-strand breaks generated after Top1 proteolysis and before Tdp1 action. Analysis of DSB signalling reveals a novel function of DNA-PK in promoting protein ubiquitination leading (i) to full ATM activity at DSB sites by promoting H2AX and H2A…
Advisors/Committee Members: Sordet, Olivier (thesis director).
Subjects/Keywords: Topoisomérase; Cassures double-brin; DNA-PK; Ubiquitine; Camptothécine; Transcription; Tdp1; Dommage à l'ADN; Topoisomerase; Double-strand breaks; DNA-PK; Ubiquitin; Camptothecin; Transcription; Tdp1; DNA damage
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Cristini, A. (2015). DNA double-strand break formation and signalling in response to transcription-blocking topoisomerase I complexes : Formation et signalisation des cassures double-brin de l'ADN lors d'un blocage de la transcription. (Doctoral Dissertation). Université Toulouse III – Paul Sabatier. Retrieved from http://www.theses.fr/2015TOU30276
Chicago Manual of Style (16th Edition):
Cristini, Agnese. “DNA double-strand break formation and signalling in response to transcription-blocking topoisomerase I complexes : Formation et signalisation des cassures double-brin de l'ADN lors d'un blocage de la transcription.” 2015. Doctoral Dissertation, Université Toulouse III – Paul Sabatier. Accessed April 17, 2021.
http://www.theses.fr/2015TOU30276.
MLA Handbook (7th Edition):
Cristini, Agnese. “DNA double-strand break formation and signalling in response to transcription-blocking topoisomerase I complexes : Formation et signalisation des cassures double-brin de l'ADN lors d'un blocage de la transcription.” 2015. Web. 17 Apr 2021.
Vancouver:
Cristini A. DNA double-strand break formation and signalling in response to transcription-blocking topoisomerase I complexes : Formation et signalisation des cassures double-brin de l'ADN lors d'un blocage de la transcription. [Internet] [Doctoral dissertation]. Université Toulouse III – Paul Sabatier; 2015. [cited 2021 Apr 17].
Available from: http://www.theses.fr/2015TOU30276.
Council of Science Editors:
Cristini A. DNA double-strand break formation and signalling in response to transcription-blocking topoisomerase I complexes : Formation et signalisation des cassures double-brin de l'ADN lors d'un blocage de la transcription. [Doctoral Dissertation]. Université Toulouse III – Paul Sabatier; 2015. Available from: http://www.theses.fr/2015TOU30276
University of Washington
6.
Burleigh, Katelyn.
Human DNA-PK activates a STING-independent DNA sensing pathway.
Degree: PhD, 2019, University of Washington
URL: http://hdl.handle.net/1773/44396
► Recognition of foreign nucleic acids is critical for antiviral defense. Detection of DNA is mediated by the cGAS-STING pathway, which activates a potent type I…
(more)
▼ Recognition of foreign nucleic acids is critical for antiviral defense. Detection of
DNA is mediated by the cGAS-STING pathway, which activates a potent type I interferon response. This pathway is broadly required for antiviral defense across cell types and species, and its relevance in context of infection, cancer, and autoimmunity has been thoroughly established. However, we have discovered an additional STING-independent
DNA sensing pathway (SIDSP) in human cells. Using STING KO human cell lines, we find that the induction of interferon is indeed abrogated at early timepoints, but surprisingly, at later timepoints, we observe a robust
DNA-induced interferon response. Here we identify
DNA-
PK as the sensor for the SIDSP and demonstrate that its kinase activity is required for the antiviral response. We show that a heat shock protein HSPA8/HSC70 is phosphorylated after
DNA stimulation and acts as a marker for the SIDSP. Finally, we explore how
DNA viruses antagonize both the cGAS-STING pathway and the SIDSP. Our work highlights the importance of nucleic acid sensing for both host and virus and has implications for modulating
DNA sensing in order to improve therapies for cancer or autoimmunity.
Advisors/Committee Members: Stetson, Daniel B (advisor).
Subjects/Keywords: cGAS-STING; DNA-PK; DNA sensing; HSPA8; STING-independent DNA sensing pathway; type I interferons; Immunology; Molecular and cellular biology
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Burleigh, K. (2019). Human DNA-PK activates a STING-independent DNA sensing pathway. (Doctoral Dissertation). University of Washington. Retrieved from http://hdl.handle.net/1773/44396
Chicago Manual of Style (16th Edition):
Burleigh, Katelyn. “Human DNA-PK activates a STING-independent DNA sensing pathway.” 2019. Doctoral Dissertation, University of Washington. Accessed April 17, 2021.
http://hdl.handle.net/1773/44396.
MLA Handbook (7th Edition):
Burleigh, Katelyn. “Human DNA-PK activates a STING-independent DNA sensing pathway.” 2019. Web. 17 Apr 2021.
Vancouver:
Burleigh K. Human DNA-PK activates a STING-independent DNA sensing pathway. [Internet] [Doctoral dissertation]. University of Washington; 2019. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/1773/44396.
Council of Science Editors:
Burleigh K. Human DNA-PK activates a STING-independent DNA sensing pathway. [Doctoral Dissertation]. University of Washington; 2019. Available from: http://hdl.handle.net/1773/44396
Duke University
7.
Li, Shenduo.
Nuclear Basic Fibroblast Growth Factor Regulation of Triple-Negative Breast Cancer Dormancy/Recurrence
.
Degree: 2014, Duke University
URL: http://hdl.handle.net/10161/9411
► Chemotherapy remains the only available treatment for triple-negative (TN) breast cancer. Although some TN breast cancers respond initially to neoadjuvant chemotherapy, the majority of…
(more)
▼ Chemotherapy remains the only available treatment for triple-negative (TN) breast cancer. Although some TN breast cancers respond initially to neoadjuvant chemotherapy, the majority of patients die within three years of treatment due to recurrent tumor growth. Developing ex vivo models for TN breast cancer recurrence and defining responsible molecules will be crucial to developing effective combination therapies for TN breast cancer patients. We have developed an in vitro model of TN breast cancer dormancy/recurrence. Short-term exposure of tumor cells to chemotherapy at clinically relevant doses enriches for a dormant tumor cell population. Several days after removing chemotherapy, dormant tumor cells regain proliferative ability and establish colonies, resembling tumor recurrence. Tumor cells from "recurrent" colonies exhibit increased chemotherapy resistance, resembling therapy resistance of recurrent tumors in patients. Furthermore, we identify a novel signaling axis [nuclear bFGF/
DNA-dependent protein kinase (
DNA-
PK)] supported by chemotherapy-enriched dormant TN breast cancer cells. This signaling axis drives accelerated
DNA repair in chemo-residual TN breast cancer cells. Targeting this axis with either with a bFGF shRNA or
DNA-
PK small molecule inhibitor blocks recurrent colony formation. Using the Oncomine gene expression database, we found that bFGF expression in tumor samples from TN breast cancer patients predicts five year tumor recurrence following neoadjuvant chemotherapy treatment. Finally, we demonstrate that recurrent tumor cells exhibit increased invasiveness, reflecting the aggressive behavior of recurrent tumors in patients. Collectively, these studies identify a novel signaling axis in TN breast cancer that likely contributes to tumor recurrence and provide molecular targets for developing future therapeutics against TN breast cancer.
Advisors/Committee Members: Bachelder, Robin E (advisor), Pizzo, Salvatore V (advisor).
Subjects/Keywords: Pathology;
breast cancer;
cancer biology;
DNA-PK;
FGF-2;
recurrence;
triple-negative breast cancer
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Li, S. (2014). Nuclear Basic Fibroblast Growth Factor Regulation of Triple-Negative Breast Cancer Dormancy/Recurrence
. (Thesis). Duke University. Retrieved from http://hdl.handle.net/10161/9411
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Li, Shenduo. “Nuclear Basic Fibroblast Growth Factor Regulation of Triple-Negative Breast Cancer Dormancy/Recurrence
.” 2014. Thesis, Duke University. Accessed April 17, 2021.
http://hdl.handle.net/10161/9411.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Li, Shenduo. “Nuclear Basic Fibroblast Growth Factor Regulation of Triple-Negative Breast Cancer Dormancy/Recurrence
.” 2014. Web. 17 Apr 2021.
Vancouver:
Li S. Nuclear Basic Fibroblast Growth Factor Regulation of Triple-Negative Breast Cancer Dormancy/Recurrence
. [Internet] [Thesis]. Duke University; 2014. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/10161/9411.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Li S. Nuclear Basic Fibroblast Growth Factor Regulation of Triple-Negative Breast Cancer Dormancy/Recurrence
. [Thesis]. Duke University; 2014. Available from: http://hdl.handle.net/10161/9411
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Université de Sherbrooke
8.
Chatterjee, Rachita.
DNA-PK sustains autophagy and pancreatic cancer cell growth: DNA-PK supporte l’autophagie et la croissance des cellules pancréatiques tumorales.
Degree: 2021, Université de Sherbrooke
URL: http://hdl.handle.net/11143/17874
► Selon les récentes statistiques, le cancer pancréatique est la quatrième cause de décès par cancer au Canada avec une survie à 5 ans de 8%.…
(more)
▼ Selon les récentes statistiques, le cancer pancréatique est la quatrième cause de décès par cancer au Canada avec une survie à 5 ans de 8%. Le cancer du pancréas réfère à l'adénocarcinome canalaire pancréatique (PDAC) qui représente près de 85% des cas diagnostiqués. Actuellement, la gemcitabine demeure la première ligne de traitement du PDAC malgré une efficacité limitée. Il est connu que la gemcitabine provoque des dommages à l'ADN en provoquant des cassures double-brin. Ces cassures peuvent être réparées par la voie de réparation de jonction d'extrémités non-homologues, la
DNA-
PK y jouant un rôle clé. Il a été observé que les tissus PDAC présentent des niveaux d’expression élevés de la
DNA-PKcs. De plus, il a été suggéré que la
DNA-
PK soutient la croissance des cellules PDAC. Les mécanismes impliqués demeurent toutefois mal étudiés. Récemment, il a été démontré que l'autophagie joue un rôle important dans la croissance des cellules PDAC. Dans certains types de cancer, la
DNA-
PK a été proposée comme une régulatrice de l’autophagie. Ainsi, nous avons entrepris cette étude en émettant l'hypothèse que la
DNA-
PK soutient l'autophagie et la croissance des cellules PDAC. Les lignées cellulaires PDAC MIA PaCa-2 et PANC1 ont été utilisées comme modèles d'étude. L'inhibiteur spécifique de la
DNA-
PK, le NU7441, a été exploitée pour explorer le rôle de la
DNA-
PK dans la croissance et l’autophagie des cellules PDAC. Une réduction, dépendante de la dose et du temps, de la croissance des cellules PDAC a été observée lors du traitement au NU7441. L'inhibition de la
DNA-
PK a également restreint la capacité des cellules PDAC à former des colonies lors d’essais de clonogénicité. Le traitement au NU7441 a provoqué un clivage de PARP et de la caspase-7 suggérant que l’inhibition de la
DNA-
PK induit l'apoptose. Le traitement au NU7441 a mené à une accumulation des niveaux de marqueurs d'autophagie soient LC3B II et p62. La mesure du flux autophagique a confirmé que cette accumulation était due au blocage de l'autophagie. Dans l'ensemble, l'étude révèle que la
DNA-
PK abroge la croissance des cellules PDAC corrélant avec un blocage de l'autophagie. Les mécanismes empruntés par la
DNA-
PK pour réguler l’autophagie demeurent à être identifiés, ce qui pourrait permettre de caractériser de nouvelles cibles visant à optimiser la réponse des cellules PDAC à la gemcitabine.
Advisors/Committee Members: Boucher, Marie-Josée (advisor).
Subjects/Keywords: Pancreatic cancer; DNA-PK; Autophagy; NU7441; Cell growth; Treatment; Cancer pancréatique; Autophagie; Croissance cellulaire; Traitement
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Chatterjee, R. (2021). DNA-PK sustains autophagy and pancreatic cancer cell growth: DNA-PK supporte l’autophagie et la croissance des cellules pancréatiques tumorales. (Masters Thesis). Université de Sherbrooke. Retrieved from http://hdl.handle.net/11143/17874
Chicago Manual of Style (16th Edition):
Chatterjee, Rachita. “DNA-PK sustains autophagy and pancreatic cancer cell growth: DNA-PK supporte l’autophagie et la croissance des cellules pancréatiques tumorales.” 2021. Masters Thesis, Université de Sherbrooke. Accessed April 17, 2021.
http://hdl.handle.net/11143/17874.
MLA Handbook (7th Edition):
Chatterjee, Rachita. “DNA-PK sustains autophagy and pancreatic cancer cell growth: DNA-PK supporte l’autophagie et la croissance des cellules pancréatiques tumorales.” 2021. Web. 17 Apr 2021.
Vancouver:
Chatterjee R. DNA-PK sustains autophagy and pancreatic cancer cell growth: DNA-PK supporte l’autophagie et la croissance des cellules pancréatiques tumorales. [Internet] [Masters thesis]. Université de Sherbrooke; 2021. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/11143/17874.
Council of Science Editors:
Chatterjee R. DNA-PK sustains autophagy and pancreatic cancer cell growth: DNA-PK supporte l’autophagie et la croissance des cellules pancréatiques tumorales. [Masters Thesis]. Université de Sherbrooke; 2021. Available from: http://hdl.handle.net/11143/17874
9.
Heberle, Eléa.
Etude du rôle et de la régulation de la Poly(ADP-ribose) Glycohydrolase(PARG) dans la réponse cellulaire aux dommages à l'ADN : Role and regulation of the Poly(ADP-ribose)Glycohydrolase (PARG) in the cell response to DNA damages.
Degree: Docteur es, Aspects moléculaires et cellulaires de la biologie, 2017, Université de Strasbourg
URL: http://www.theses.fr/2017STRAJ106
► La Poly(ADP-ribosyl)ation est une modification post-traductionnelle de protéines, impliquée dans un grand nombre de processus biologiques, dont la réparation de l’ADN. Alors que la fonction…
(more)
▼ La Poly(ADP-ribosyl)ation est une modification post-traductionnelle de protéines, impliquée dans un grand nombre de processus biologiques, dont la réparation de l’ADN. Alors que la fonction et le mode d’action de la Poly(ADP-ribose) (PAR) Polymérase 1 (PARP1), activée en réponse aux dommages de l’ADN sont bien compris, on en sait beaucoup moins sur la fonction et la régulation de l’enzyme de dégradation du PAR, la Poly(ADP-ribose) glycohydrolase (PARG). Dans le contexte de ce projet de thèse, nous décrivons de nouvelles lignées U2OS stables, déficientes pour toutes les isoformes de PARG, permettant la complémentation inductible avec chacun des isoformes de PARG. Ces modèles nous ont permis d’évaluer les contributions relatives des isoformes à la réparation de dommages à l’ADN. Nous avons identifié un nouveau partenaire cellulaire de PARG : la protéine-kinase dépendante des dommages à l’ADN (DNA-PK). Nous explorons l’interaction fonctionnelle de ces deux protéines dans le contexte de la réponse cellulaire à la camptothécine (CPT), un agent anticancéreux inhibant la topoisomérase I et provoquant l’activation simultanée de PARP1 et DNA-PK.
Poly (ADP-ribosyl) ation is a post-translational modification of proteins involved in a large number of biological processes, including DNA repair. While the function and mode of action of Poly (ADP-ribose) (PAR) Polymerase 1 (PARP1), activated in response to DNA damage, is well understood, much less is known about the function and regulation the PAR degrading enzyme, Poly (ADP-ribose) glycohydrolase (PARG). In the context of this thesis project, we describe new stable U2OS lines, deficient for all PARG isoforms, allowing the inducible complementation with each of the PARG isoforms. These models allowed us to evaluate the relative contributions of the isoforms to DNA damage repair. We have identified a new cellular partner of PARG: the DNA-dependent protein kinase-dependent kinase (DNA-PK). We explore the functional interaction between these two proteins in the context of the cellular response to camptothecin (CPT), an anticancer drug that inhibits topoisomerase I and induces the simultaneous activation of PARP1 and DNA-PK.
Advisors/Committee Members: Schreiber, Valérie (thesis director).
Subjects/Keywords: Poly(ADP-ribose); PAR; PARG; DNA-PK; Régulation; Isoformes; Réponse aux dommages à l’ADN; Réparation; Réplication; Phosphorylation; Modification post-traductionnelle; Poly(ADP-ribose); PAR; PARG; DNA-PK; Régulation; Isoformes; DNA damage response; Repair; Replication; Phosphorylation; Post-translational modification; 572.4; 572.8
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Heberle, E. (2017). Etude du rôle et de la régulation de la Poly(ADP-ribose) Glycohydrolase(PARG) dans la réponse cellulaire aux dommages à l'ADN : Role and regulation of the Poly(ADP-ribose)Glycohydrolase (PARG) in the cell response to DNA damages. (Doctoral Dissertation). Université de Strasbourg. Retrieved from http://www.theses.fr/2017STRAJ106
Chicago Manual of Style (16th Edition):
Heberle, Eléa. “Etude du rôle et de la régulation de la Poly(ADP-ribose) Glycohydrolase(PARG) dans la réponse cellulaire aux dommages à l'ADN : Role and regulation of the Poly(ADP-ribose)Glycohydrolase (PARG) in the cell response to DNA damages.” 2017. Doctoral Dissertation, Université de Strasbourg. Accessed April 17, 2021.
http://www.theses.fr/2017STRAJ106.
MLA Handbook (7th Edition):
Heberle, Eléa. “Etude du rôle et de la régulation de la Poly(ADP-ribose) Glycohydrolase(PARG) dans la réponse cellulaire aux dommages à l'ADN : Role and regulation of the Poly(ADP-ribose)Glycohydrolase (PARG) in the cell response to DNA damages.” 2017. Web. 17 Apr 2021.
Vancouver:
Heberle E. Etude du rôle et de la régulation de la Poly(ADP-ribose) Glycohydrolase(PARG) dans la réponse cellulaire aux dommages à l'ADN : Role and regulation of the Poly(ADP-ribose)Glycohydrolase (PARG) in the cell response to DNA damages. [Internet] [Doctoral dissertation]. Université de Strasbourg; 2017. [cited 2021 Apr 17].
Available from: http://www.theses.fr/2017STRAJ106.
Council of Science Editors:
Heberle E. Etude du rôle et de la régulation de la Poly(ADP-ribose) Glycohydrolase(PARG) dans la réponse cellulaire aux dommages à l'ADN : Role and regulation of the Poly(ADP-ribose)Glycohydrolase (PARG) in the cell response to DNA damages. [Doctoral Dissertation]. Université de Strasbourg; 2017. Available from: http://www.theses.fr/2017STRAJ106
University of Southern California
10.
Li, Angela Ying-Jian.
Molecular analysis of high mobility group A2 (HMGA2)
oncogenic function.
Degree: PhD, Pharmaceutical Sciences, 2008, University of Southern California
URL: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/86635/rec/4176
► HMGA2 is located on chromosome 12q13-15, which is frequently amplified or subjected to chromosomal rearrangements in human cancers. However, the multitudinous tumorigenic roles of HMGA2…
(more)
▼ HMGA2 is located on chromosome 12q13-15, which is
frequently amplified or subjected to chromosomal rearrangements in
human cancers. However, the multitudinous tumorigenic roles of
HMGA2 remain elusive. In our first study, we provide molecular and
cellular evidence that HMGA2 forms complexes with Ku70/80-
DNA,
hence conferring deficiency in overall and precise NHEJ-mediated
DNA repair. This is reflected by a prolonged duration of
DNA-PKcs
phosphorylation at Ser-2956 and Thr-2609 in response to
DNA damage.
Consequently, HMGA2 alone is sufficient to induce spontaneous
chromosome aberrations in WI-38 cells. Using real-time imaging in
living cells, a sustained accumulation of
DNA-PKcs at DSB sites in
HMGA2-expressing cells receiving microirradiation was observed,
resembling to observations found among
DNA-PKcs mutants.
Furthermore, knocking down HMGA2 or abolishing HMGA2-
DNA
interaction reverses HMGA2-elicited dysregulation of
DNA-PKcs
activation profile and the enhanced susceptibility to DSBs. Lastly,
HMGA2 expression correlates with unfavorable treatment outcome in
breast cancer. Together, these results support a model in which the
interplay between Ku70/80 and HMGA2 interferes with NHEJ and shed
light on a novel role of HMGA2 in promoting genome instability.;
Human telomerase activity is tightly regulated by the expression of
hTERT and reactivation of telomerase is required for most
neoplasia. In our second study, Affymetrix microarray gene
expression analyses indicate an inverse co-regulation of hTERT and
HDAC4 by HMGA2 in HeLa cells. Functionally, HMGA2 conveys
significantly lower HDAC activities, enhanced basal telomerase
activities, and resistance to two different classes of telomerase
inhibitors. Co-transfection of HMGA2 or treatment with SAHA, an
HDAC inhibitor, renders hTERT-reporter activation in a
dose-dependent manner. Furthermore, HMGA2 expression results in
increased localized H3-K9acetylation in hTERT proximal promoter via
HDAC4 downregulation and/or proteinprotein interaction of HMGA2
with Sp1 or HDAC4. Observations on the reactivation of telomerase
activity in WI-38 cells transduced with lenti-HMGA2 and a positive
correlation between the expression levels of HMGA2 and hTERT
(p=0.01) from 34 breast cancer patient samples further confirm a
critical role for HMGA2 to induce hTERT expression. Together, we
propose that a combination of downregulating HDAC4 expression,
hence activity and decreased recruitment of HDAC4 through Sp1 to
hTERT promoter, are exploited by HMGA2 during
oncogenesis.
Advisors/Committee Members: Wang, Clay C. C. (Committee Chair), Ann, David K. (Committee Member), Hacia, Joseph G. (Committee Member), Haworth, Ian (Committee Member), Shen, Wei-Chiang (Committee Member).
Subjects/Keywords: HMGA2; NHEJ; DNA-PK; DSBs; hTERT; telomere
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Li, A. Y. (2008). Molecular analysis of high mobility group A2 (HMGA2)
oncogenic function. (Doctoral Dissertation). University of Southern California. Retrieved from http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/86635/rec/4176
Chicago Manual of Style (16th Edition):
Li, Angela Ying-Jian. “Molecular analysis of high mobility group A2 (HMGA2)
oncogenic function.” 2008. Doctoral Dissertation, University of Southern California. Accessed April 17, 2021.
http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/86635/rec/4176.
MLA Handbook (7th Edition):
Li, Angela Ying-Jian. “Molecular analysis of high mobility group A2 (HMGA2)
oncogenic function.” 2008. Web. 17 Apr 2021.
Vancouver:
Li AY. Molecular analysis of high mobility group A2 (HMGA2)
oncogenic function. [Internet] [Doctoral dissertation]. University of Southern California; 2008. [cited 2021 Apr 17].
Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/86635/rec/4176.
Council of Science Editors:
Li AY. Molecular analysis of high mobility group A2 (HMGA2)
oncogenic function. [Doctoral Dissertation]. University of Southern California; 2008. Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/86635/rec/4176
Université Paris-Sud – Paris XI
11.
Croset, Amélie.
Identification et caractérisation des mécanismes d'action des molécules appats, les SiDNA, dans l'inhibition des voies de réparation des cassures simple-brin : Identification and characterization of bait molecules mechanisms of action, the SIDNA, in the inhibition of single strand break repair pathway.
Degree: Docteur es, Cancérologie, radiobiologie, 2013, Université Paris-Sud – Paris XI
URL: http://www.theses.fr/2013PA11T018
► La plupart des traitements anticancéreux, comme la chimiothérapie ou la radiothérapie, sont cytotoxiques et causent des dommages à l'ADN dans le but d’induire la mort…
(more)
▼ La plupart des traitements anticancéreux, comme la chimiothérapie ou la radiothérapie, sont cytotoxiques et causent des dommages à l'ADN dans le but d’induire la mort des cellules tumorales. Cependant, l’efficacité d’activité de réparation de l'ADN des tumeurs entraine des résistances intrinsèques et acquises aux traitements. L'une des étapes précoces de la réparation de l’ADN est le recrutement de protéines au niveau du site de dommage. Ce recrutement est coordonné par une cascade de modifications et est contrôlé par des protéines senseurs telles que la protéine kinase ADN dépendante (DNA-PK) et / ou la poly (ADP- ribose) polymérase (PARP). Dans ce manuscrit, nous avons identifié et caractérisé le mécanisme d'action de petites molécules d'ADN (les siDNA), mimant des cassures double brin (appelé Dbait) ou simple brin (appelé Pbait), dans l’inhibition des voies de réparation des cassures simple brin (SSBR/BER). Nous démontrons que les molécules Dbait recrutent et activent à la fois PARP et DNA-PK, contrairement aux molécules Pbait qui ne recrutent que la PARP. L'étude comparative de ces deux molécules permet d'analyser les rôles respectifs des deux voies de signalisation: les deux molécules recrutent les protéines impliquées dans la voie de réparation des cassures simple brin (comme PARP, PCNA et XRCC1) et empêchent leurs recrutements aux niveaux des lésions chromosomiques. Les molécules Dbait inhibent par ailleurs le recrutement des protéines impliquées dans la voie de réparation des cassures double brin (NHEJ et HR). Pbait et Dbait désorganisent la réparation de l’ADN et sensibilisent les cellules tumorales aux traitements. L’inhibition de la réparation des cassures simple brin semble dépendre d’un piégeage des protéines directement sur les siDNA ou indirectement sur les polymères PAR. L’inhibition des voies de réparation des cassures double brin (DSB) semble par contre se faire de façon indirecte ; cette inhibition résulterait plutôt de la phosphorylation des protéines de réparation des DSB de part l’activation de DNA-PK. Les molécules Dbait et Pbait induisent un effet de létalité synthétique des cellules tumorales BRCA mutées. Cependant, la mutation BRCA semble être suffisante mais non nécessaire pour induire la sensibilité des cellules tumorales aux traitements Dbait. En effet, nous avons démontré que les molécules Dbait peuvent aussi sensibiliser les cellules ne présentant pas de mutation BRCA mais ayant toutefois une forte instabilité génétique. Nous avons trouvé une corrélation entre le niveau basal de protéines de réparation de l'ADN (ɣH2AX, PARP et PAR), le taux basal de cassures à l’ADN, la présence de micronoyaux (MN) et la sensibilité des cellules tumorales au traitement Dbait. Nous avons émis l’hypothèse que cette instabilité génétique, déterminé par la quantification de MN dans des biopsies tumorales, pourrait être un biomarqueur prédictif de l’effet du Dbait, non seulement dans les cancers du sein, mais aussi dans les glioblastomes, les mélanomes, les mélanomes uvéaux et les cancers du côlon.
Most…
Advisors/Committee Members: Dutreix, Marie (thesis director).
Subjects/Keywords: SiDNA; Inhibiteurs des voies de réparation de l’ADN; Poly Adenosine Diphosphate Ribose Polymerase (PARP); Protéine Kinase ADN Dépendant (DNA-PK); Signalisation des dommages à l'ADN; Protéines BRCA; Instabilité génétique; Traitement des Cancers; SiDNA; DNA Repair Inhibitors; Poly Adenosine Diphosphate Ribose Polymerase (PARP); DNA-Activated Protein Kinase (DNA-PK); DNA Damage Signaling; BReast CAncer; Genetic Instability; Cancer Treatement
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Croset, A. (2013). Identification et caractérisation des mécanismes d'action des molécules appats, les SiDNA, dans l'inhibition des voies de réparation des cassures simple-brin : Identification and characterization of bait molecules mechanisms of action, the SIDNA, in the inhibition of single strand break repair pathway. (Doctoral Dissertation). Université Paris-Sud – Paris XI. Retrieved from http://www.theses.fr/2013PA11T018
Chicago Manual of Style (16th Edition):
Croset, Amélie. “Identification et caractérisation des mécanismes d'action des molécules appats, les SiDNA, dans l'inhibition des voies de réparation des cassures simple-brin : Identification and characterization of bait molecules mechanisms of action, the SIDNA, in the inhibition of single strand break repair pathway.” 2013. Doctoral Dissertation, Université Paris-Sud – Paris XI. Accessed April 17, 2021.
http://www.theses.fr/2013PA11T018.
MLA Handbook (7th Edition):
Croset, Amélie. “Identification et caractérisation des mécanismes d'action des molécules appats, les SiDNA, dans l'inhibition des voies de réparation des cassures simple-brin : Identification and characterization of bait molecules mechanisms of action, the SIDNA, in the inhibition of single strand break repair pathway.” 2013. Web. 17 Apr 2021.
Vancouver:
Croset A. Identification et caractérisation des mécanismes d'action des molécules appats, les SiDNA, dans l'inhibition des voies de réparation des cassures simple-brin : Identification and characterization of bait molecules mechanisms of action, the SIDNA, in the inhibition of single strand break repair pathway. [Internet] [Doctoral dissertation]. Université Paris-Sud – Paris XI; 2013. [cited 2021 Apr 17].
Available from: http://www.theses.fr/2013PA11T018.
Council of Science Editors:
Croset A. Identification et caractérisation des mécanismes d'action des molécules appats, les SiDNA, dans l'inhibition des voies de réparation des cassures simple-brin : Identification and characterization of bait molecules mechanisms of action, the SIDNA, in the inhibition of single strand break repair pathway. [Doctoral Dissertation]. Université Paris-Sud – Paris XI; 2013. Available from: http://www.theses.fr/2013PA11T018
University of Cincinnati
12.
Kavanaugh, Gina M.
The Role of the Human DEK Oncogene in the Regulation of DNA
Damage Response and Repair.
Degree: PhD, Medicine: Cell and Molecular Biology, 2011, University of Cincinnati
URL: http://rave.ohiolink.edu/etdc/view?acc_num=ucin1305893047
► Altered chromatin integrity and improper DNA damage repair are commonly associated with the formation and progression of human cancers. Here, we investigate the contribution of…
(more)
▼ Altered chromatin integrity and improper
DNA damage
repair are commonly associated with the formation and progression
of human cancers. Here, we investigate the contribution of the DEK
oncogene – elevated in numerous human cancers – to
DNA damage
repair and chromatin stability. Initially, studies examining the
effect of DEK loss demonstrated an accumulation of low levels of
DNA damage markers in human cancer cells and xenografts, suggesting
a deficiency in
DNA damage repair. Importantly, DEK depletion led
to alterations in
DNA damage kinase response pathways. ATM pathway
activation was increased, accounting for the elevated levels of
H2AX phosphorylation observed in DEK deficient cells.
Alternatively,
DNA-
PK phosphorylation and kinase activity were
reduced with DEK loss. Similar
DNA damage responses were observed
in primary Dek knockout mouse embryonic fibroblasts (MEFs), along
with increased levels of
DNA damage and exaggerated induction of
senescence in response to genotoxic stress. Importantly, Dek
knockout MEFs exhibited distinct defects in non-homologous
end-joining (NHEJ), micro-homology mediated end-joining (MMEJ), and
homologous recombination (HR) repair when compared to their wild
type counterparts. Notably, DEK-depleted Hela cells exhibited
reduced levels of histone H2B ubiquitination. Histone modifications
play an important role in genome topology and
DNA damage repair.
Additionally, H2B ubiquitination was recently reported to be
required for the recruitment of NHEJ and HR components. We
therefore hypothesize that DEK plays a role upstream of the
DNA
damage response as a regulator of chromatin stability and topology.
Future studies concentrating on the contribution of DEK to genome
integrity may reveal possible molecular DEK targets for the
development of cancer therapeutics.
Advisors/Committee Members: Wells, Susanne (Committee Chair).
Subjects/Keywords: Molecular Biology; DEK; DNA-PK; NHEJ; DNA damage repair; histone modification
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Kavanaugh, G. M. (2011). The Role of the Human DEK Oncogene in the Regulation of DNA
Damage Response and Repair. (Doctoral Dissertation). University of Cincinnati. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=ucin1305893047
Chicago Manual of Style (16th Edition):
Kavanaugh, Gina M. “The Role of the Human DEK Oncogene in the Regulation of DNA
Damage Response and Repair.” 2011. Doctoral Dissertation, University of Cincinnati. Accessed April 17, 2021.
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1305893047.
MLA Handbook (7th Edition):
Kavanaugh, Gina M. “The Role of the Human DEK Oncogene in the Regulation of DNA
Damage Response and Repair.” 2011. Web. 17 Apr 2021.
Vancouver:
Kavanaugh GM. The Role of the Human DEK Oncogene in the Regulation of DNA
Damage Response and Repair. [Internet] [Doctoral dissertation]. University of Cincinnati; 2011. [cited 2021 Apr 17].
Available from: http://rave.ohiolink.edu/etdc/view?acc_num=ucin1305893047.
Council of Science Editors:
Kavanaugh GM. The Role of the Human DEK Oncogene in the Regulation of DNA
Damage Response and Repair. [Doctoral Dissertation]. University of Cincinnati; 2011. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=ucin1305893047
Queensland University of Technology
13.
Ashton, Nicholas W.
Characterisation of human single-stranded DNA-binding protein 1 (hSSB1) regulation by post-translational modifications.
Degree: 2016, Queensland University of Technology
URL: https://eprints.qut.edu.au/98660/
► Human single-stranded DNA-binding protein 1 (hSSB1) is required for the timely repair of double-strand DNA breaks, as well as the stabilisation and restart of stalled…
(more)
▼ Human single-stranded DNA-binding protein 1 (hSSB1) is required for the timely repair of double-strand DNA breaks, as well as the stabilisation and restart of stalled replication forks. In this work, evidence is provided that cellular survival in response to replication stress is promoted by dynamic phosphorylation of hSSB1 by the DNA-dependent protein kinase (DNA-PK) and PPP-family protein phosphatases. These data provide insight into the functional regulation of hSSB1 following replication fork disruption.
Subjects/Keywords: Human single-stranded DNA-binding protein 1; Nucleic acid-binding protein 2; OB-fold containing protein 2B; Sensor of single-stranded DNA complex subunit B; DNA-dependent protein kinase (DNA-PK); PPP-family protein phosphatases; Integrator complex subunit 3 (INTS3); hSSB1; NABP2; OBFC2B
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Ashton, N. W. (2016). Characterisation of human single-stranded DNA-binding protein 1 (hSSB1) regulation by post-translational modifications. (Thesis). Queensland University of Technology. Retrieved from https://eprints.qut.edu.au/98660/
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Ashton, Nicholas W. “Characterisation of human single-stranded DNA-binding protein 1 (hSSB1) regulation by post-translational modifications.” 2016. Thesis, Queensland University of Technology. Accessed April 17, 2021.
https://eprints.qut.edu.au/98660/.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Ashton, Nicholas W. “Characterisation of human single-stranded DNA-binding protein 1 (hSSB1) regulation by post-translational modifications.” 2016. Web. 17 Apr 2021.
Vancouver:
Ashton NW. Characterisation of human single-stranded DNA-binding protein 1 (hSSB1) regulation by post-translational modifications. [Internet] [Thesis]. Queensland University of Technology; 2016. [cited 2021 Apr 17].
Available from: https://eprints.qut.edu.au/98660/.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Ashton NW. Characterisation of human single-stranded DNA-binding protein 1 (hSSB1) regulation by post-translational modifications. [Thesis]. Queensland University of Technology; 2016. Available from: https://eprints.qut.edu.au/98660/
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
14.
Chalasani, Sri Lakshmi.
RESOLUTION OF PROXIMAL OXIDATIVE BASE DAMAGE AND 3′-PHOSPHATE TERMINI FOR NONHOMOLOGOUS END JOINING OF FREE RADICAL-MEDIATED DNA DOUBLE-STRAND BREAKS.
Degree: PhD, Pharmacology & Toxicology, 2018, Virginia Commonwealth University
URL: https://doi.org/10.25772/KQ3H-CN65
;
https://scholarscompass.vcu.edu/etd/5237
► Clustered damage to DNA is a signature mark of radiation-induced damage, which involves damage to the nucleobases and/or DNA backbone. Double-strand breaks created by…
(more)
▼ Clustered damage to
DNA is a signature mark of radiation-induced damage, which involves damage to the nucleobases and/or
DNA backbone. Double-strand breaks created by damaging agents are detrimental to cell survival leading to chromosomal translocations. Normal cells employ Non-homologous end-joining because of its faster kinetics, to suppress chromosomal translocations. However, the presence of complex
DNA ends constitutes a significant challenge to NHEJ. Location of Thymine glycol (Tg) at DSB ends was a potential hindrance to end joining. The substrate with Tg at the third position (Tg3) from the DSB joined better than when present at the fifth position (Tg5). However, hNTH1 assay showed Tg5 to be a better substrate than Tg3 for BER, potentially explaining the increased Tg removal and decreased end joining of Tg5 in extracts. Nonetheless, there appeared to be no preference in the susceptibility of 5’-Tg substrates with Tg at the second and third positions from DSB ends.
Polynucleotide kinase phosphatase is crucial in restoring the 3′ hydroxyl, and 5′ phosphate ends at strand breaks. No other enzyme is known to possess PNKP’s activity in mammalian cells at DSBs. Experiments done with PNKP knockout cells have shown some activity similar to PNKP, which appeared to be a part of NHEJ and was not pharmacologically inhibited by PNKP inhibitor. Additionally, core NHEJ factors XRCC4 and XLF influenced the activities of PNKP.
Overall, these experiments suggest that Tg repair is dependent on the position from DSB and an alternative enzyme processes 3′- PO, and 5′-OH ends.
Advisors/Committee Members: Lawrence F Povirk.
Subjects/Keywords: NHEJ; BER; hNTH1; Thymine glycol; PNKP; DNA-PK; XLF
…9.1: Role of DNA-PK in NHEJ and DNA DSB processing …... 136
Fig. 9.2: Role of XLF-XRCC4… …response
DNA
Deoxyribonucleic acid
DNA - PK
DNA-dependent protein kinase
DNA - PKcs
DNA… …cell lines. NU7441, a DNA-PK inhibitor significantly blocked the
activity in both wild-type… …core NHEJ proteins that form DNA-dependent
protein kinase (DNA-PK). XRCC5 and XRCC6… …DNA-PK), and XRCC7 encodes the
470 kDa DNA-catalytic subunit of protein kinase DNA-PKcs…
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Chalasani, S. L. (2018). RESOLUTION OF PROXIMAL OXIDATIVE BASE DAMAGE AND 3′-PHOSPHATE TERMINI FOR NONHOMOLOGOUS END JOINING OF FREE RADICAL-MEDIATED DNA DOUBLE-STRAND BREAKS. (Doctoral Dissertation). Virginia Commonwealth University. Retrieved from https://doi.org/10.25772/KQ3H-CN65 ; https://scholarscompass.vcu.edu/etd/5237
Chicago Manual of Style (16th Edition):
Chalasani, Sri Lakshmi. “RESOLUTION OF PROXIMAL OXIDATIVE BASE DAMAGE AND 3′-PHOSPHATE TERMINI FOR NONHOMOLOGOUS END JOINING OF FREE RADICAL-MEDIATED DNA DOUBLE-STRAND BREAKS.” 2018. Doctoral Dissertation, Virginia Commonwealth University. Accessed April 17, 2021.
https://doi.org/10.25772/KQ3H-CN65 ; https://scholarscompass.vcu.edu/etd/5237.
MLA Handbook (7th Edition):
Chalasani, Sri Lakshmi. “RESOLUTION OF PROXIMAL OXIDATIVE BASE DAMAGE AND 3′-PHOSPHATE TERMINI FOR NONHOMOLOGOUS END JOINING OF FREE RADICAL-MEDIATED DNA DOUBLE-STRAND BREAKS.” 2018. Web. 17 Apr 2021.
Vancouver:
Chalasani SL. RESOLUTION OF PROXIMAL OXIDATIVE BASE DAMAGE AND 3′-PHOSPHATE TERMINI FOR NONHOMOLOGOUS END JOINING OF FREE RADICAL-MEDIATED DNA DOUBLE-STRAND BREAKS. [Internet] [Doctoral dissertation]. Virginia Commonwealth University; 2018. [cited 2021 Apr 17].
Available from: https://doi.org/10.25772/KQ3H-CN65 ; https://scholarscompass.vcu.edu/etd/5237.
Council of Science Editors:
Chalasani SL. RESOLUTION OF PROXIMAL OXIDATIVE BASE DAMAGE AND 3′-PHOSPHATE TERMINI FOR NONHOMOLOGOUS END JOINING OF FREE RADICAL-MEDIATED DNA DOUBLE-STRAND BREAKS. [Doctoral Dissertation]. Virginia Commonwealth University; 2018. Available from: https://doi.org/10.25772/KQ3H-CN65 ; https://scholarscompass.vcu.edu/etd/5237
Universidade de Lisboa
15.
Gonçalves, Maria Inês Cardoso.
O papel do DNA-PKcs na transcrição mediada pelo promotor LTR do HIV-1.
Degree: 2017, Universidade de Lisboa
URL: https://www.rcaap.pt/detail.jsp?id=oai:repositorio.ul.pt:10451/31528
► Tese de mestrado em Biologia Molecular e Genética, apresentada à Universidade de Lisboa, através da Faculdade de Ciências, 2017
O DNA-PK (Cinase dependente de DNA)…
(more)
▼ Tese de mestrado em Biologia Molecular e Genética, apresentada à Universidade de Lisboa, através da Faculdade de Ciências, 2017
O DNA-PK (Cinase dependente de DNA) é um complexo proteico nuclear que requer uma associação com o DNA para exercer a sua atividade cinásica. Este complexo é constituído por duas componentes: uma subunidade catalítica de 450 kDa (DNA-PKcs) que se trata de uma cinase de serinas e treoninas, e um heterodímero regulador designado por autoantigénio Ku composto por duas subunidades (Ku70/80). Atualmente, sabe-se que DNA-PK participa em vários processos celulares, nomeadamente ao nível do controlo da transcrição, na regulação dos genes do metabolismo celular e na manutenção dos telómeros. No entanto, a sua principal função está relacionada com a reparação de quebras de cadeia dupla no DNA, através do mecanismo NHEJ (Non-homologous end joining), que é crucial para a integridade dos linfócitos e para a reparação de quebras de dupla cadeia no DNA. Em consequência, levantou-se a hipótese do envolvimento de DNA-PK no processo de integração do provírus do HIV-1, mas os resultados
obtidos geraram controvérsia. Anteriormente, neste laboratório, surgiram evidências de que DNA-PK poderia estar envolvido na transcrição, a partir do LTR do HIV-1 (HIV-1 Long-Terminal Repeat): observou-se que o silenciamento de DNA-PKcs, através da aplicação de shRNA, resulta numa diminuição dos níveis de transcrição viral. No entanto, os mecanismos subjacentes à função deste complexo no processo de transcrição ainda estão por esclarecer. Neste estudo, examinou-se a capacidade do complexo DNA-PK modular a atividade transcricional, a partir do promotor localizado ao nível do LTR viral. Para isso, transfetaram-se células HeLa-P4 e TZM-bl com várias quantidades do plasmídeo pCMV6DNA-PKcs (0,25 e 0,5 μg) apenas ou na presença de pCMV-Tat, que expressa Tat, o transativador do LTR. Os resultados destas experiências demonstraram que DNA-PK não tem a capacidade de transativar, por si só, o LTR do HIV-1 e o promotor pCMV, existente nos plasmídeos pCMV-Tat e pCMV6DNA-PKcs. Para além disto,
observou-se um aumento dos níveis de transativação, a partir do LTR viral, na presença de pCMV-Tat e pCMV6DNA-PKcs, apenas nas células TZM-bl que têm um LTR do HIV-1 integrado completo (nt -454 a +181). As células HeLa-P4 também têm um LTR integrado mas de tamanho pequeno (nt -138 a +80), o que indica que podem existir elementos cis em falta neste LTR, necessários para a sinergia observada entre a proteína Tat e o complexo DNA-PK, no processo de transcrição, a partir do LTR do HIV-1. Para confirmar estes resultados, foram produzidos três LTR de diferentes tamanhos e posteriormente, células 293T foram transfetadas com cada um dos LTR em separado e duas quantidades de pCMV6DNA-PKcs (0,25 e 0,5 μg), apenas ou na presença de pCMV-Tat. Contrariamente aos resultados obtidos previamente, verificou-se que afinal o LTR pequeno (nt -138 a +80), presente nas células HeLa-P4, tem os elementos cis suficientes para o aumento da transativação do LTR viral, mediada…
Advisors/Committee Members: Brito, Paula Matos de, Caeiro, Filomena,1950-.
Subjects/Keywords: Vírus da Imunodeficiência Humana tipo 1 (HIV-1); Cinase dependente de DNA (DNA-PK); Transativador do LTR do HIV-1 (Tat); Elementos cis; Proteína de especificidade 1 (Pp1); Teses de mestrado - 2017; Domínio/Área Científica::Ciências Naturais::Ciências Biológicas
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Gonçalves, M. I. C. (2017). O papel do DNA-PKcs na transcrição mediada pelo promotor LTR do HIV-1. (Thesis). Universidade de Lisboa. Retrieved from https://www.rcaap.pt/detail.jsp?id=oai:repositorio.ul.pt:10451/31528
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Gonçalves, Maria Inês Cardoso. “O papel do DNA-PKcs na transcrição mediada pelo promotor LTR do HIV-1.” 2017. Thesis, Universidade de Lisboa. Accessed April 17, 2021.
https://www.rcaap.pt/detail.jsp?id=oai:repositorio.ul.pt:10451/31528.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Gonçalves, Maria Inês Cardoso. “O papel do DNA-PKcs na transcrição mediada pelo promotor LTR do HIV-1.” 2017. Web. 17 Apr 2021.
Vancouver:
Gonçalves MIC. O papel do DNA-PKcs na transcrição mediada pelo promotor LTR do HIV-1. [Internet] [Thesis]. Universidade de Lisboa; 2017. [cited 2021 Apr 17].
Available from: https://www.rcaap.pt/detail.jsp?id=oai:repositorio.ul.pt:10451/31528.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Gonçalves MIC. O papel do DNA-PKcs na transcrição mediada pelo promotor LTR do HIV-1. [Thesis]. Universidade de Lisboa; 2017. Available from: https://www.rcaap.pt/detail.jsp?id=oai:repositorio.ul.pt:10451/31528
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Freie Universität Berlin
16.
Jeblonski, Frank.
Regulation of cell cycle dependent transcription by E2F and stress pathways.
Degree: 2006, Freie Universität Berlin
URL: http://dx.doi.org/10.17169/refubium-9598
► E2F activity controls the expression of a variety of genes that encode proteins essential for DNA replication and cell cycle progression. The E2F family consists…
(more)
▼ E2F activity controls the expression of a variety of genes that encode
proteins essential for
DNA replication and cell cycle progression. The E2F
family consists of seven members containing several highly conserved domains
including the marked box . In order to identify interaction partners for E2F
that bind to the marked box, a yeast two-hybrid screen was carried out by
using a peptide of the transcription factor E2F3 comprising the marked box as
bait. This experiment identified one of the regulatory subunit of the
DNA-
PK,
called Ku70 as a binding partner. Binding of the Ku subunit to E2F proteins
has been confirmed and E2F1 and E2F3 tested to be direct targets of the
Ku70/80 heterodimer.
DNA-
PK, which is involved in the repair of
DNA double
strand breaksas well as the recombination of immunoglobin genes has recently
been shown to be involved within the cell cycle control. We tested the
regulatory function of E2F1 in relation to the
DNA-
Pk by gamma-ray induced
double strand breaks on running cell cycle. The potential functional mechanism
of that protein complex have to be determined. The results indicate a
significant reduction of E2F transactivation potential on transient
cotransfection of Ku70 and Ku80. The modulation of E2F activity by
DNA-
PK
demonstrates a key element in blocking the G1/S phase transition in the cell
cycle after
DNA damage, thereby allowing
DNA repair before replication.
Advisors/Committee Members: n (gender), Dr. Martin Lipp (firstReferee), Prof. Dr. Udo Heinemann (furtherReferee).
Subjects/Keywords: Cell cycle DNA repair E2F DNA-PK; 500 Naturwissenschaften und Mathematik::570 Biowissenschaften; Biologie::570 Biowissenschaften; Biologie
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Jeblonski, F. (2006). Regulation of cell cycle dependent transcription by E2F and stress pathways. (Thesis). Freie Universität Berlin. Retrieved from http://dx.doi.org/10.17169/refubium-9598
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Jeblonski, Frank. “Regulation of cell cycle dependent transcription by E2F and stress pathways.” 2006. Thesis, Freie Universität Berlin. Accessed April 17, 2021.
http://dx.doi.org/10.17169/refubium-9598.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Jeblonski, Frank. “Regulation of cell cycle dependent transcription by E2F and stress pathways.” 2006. Web. 17 Apr 2021.
Vancouver:
Jeblonski F. Regulation of cell cycle dependent transcription by E2F and stress pathways. [Internet] [Thesis]. Freie Universität Berlin; 2006. [cited 2021 Apr 17].
Available from: http://dx.doi.org/10.17169/refubium-9598.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Jeblonski F. Regulation of cell cycle dependent transcription by E2F and stress pathways. [Thesis]. Freie Universität Berlin; 2006. Available from: http://dx.doi.org/10.17169/refubium-9598
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
17.
Sutcu, Haser.
Implication of DNA damage and repair in viability and differentiation of muscle stem cells : Implication des dommages à l’ADN et leur réparation sur la viabilité et la différentiation des cellules souches musculaires.
Degree: Docteur es, Biologie cellulaire, 2018, Sorbonne université
URL: http://www.theses.fr/2018SORUS125
► Les cassures double-brin (DSB) sont des dommages dangereux de l’ADN et représentent un facteur de risque pour la stabilité du génome. Le maintien de l'intégrité…
(more)
▼ Les cassures double-brin (DSB) sont des dommages dangereux de l’ADN et représentent un facteur de risque pour la stabilité du génome. Le maintien de l'intégrité du génome est essentiel pour les cellules souches adultes, qui sont responsables de la régénération des tissus endommagés et de l'homéostasie tissulaire tout au long de la vie. La régénération musculaire chez l'adulte repose sur les cellules souches musculaires (cellules satellites, SCs) qui possèdent une remarquable capacité de réparation des DSB, mais dont le mécanisme sous-jacent reste inconnu. Ce projet de thèse consistait à étudier comment la différenciation musculaire est affectée lorsque la réparation des DSB est altérée, et quels sont le(s) mécanisme(s) et les conséquences de ce défaut de réparation sur la régénération musculaire. Au cours de cette étude, il est apparu de façon originale que les facteurs de réparation des DSB peuvent affecter la myogenèse, indépendamment de leur fonction dans la réparation de l'ADN. La présente étude a porté sur le rôle de la protéine kinase dépendante de l'ADN (DNA-PK), un facteur crucial pour la réparation non-homologue des DSBs (NHEJ), au cours de la différenciation musculaire chez la souris. L’étude a ciblé l'activation des SCs et la régénération musculaire in vitro et in vivo et a également abordé la régulation de cette kinase. Le rôle "canonique" de la DNA-PK, et donc du NHEJ, dans les SCs a également été étudié en présence de lésions de l'ADN radio-induites. Le rôle d’ATM, une kinase qui orchestre les réponses cellulaires aux DSB, a également été abordé dans le contexte de la régénération musculaire. Ces résultats confirment la notion émergente du rôle multifonctionnel des protéines de réparation de l’ADN dans d’autres processus physiologiques que la réparation elle-même, ce qui m’a également permis de réaliser une étude bibliographique. Ce travail i) identifie de nouveaux régulateurs de la myogenèse et ii) contribue à la compréhension de la résistance des cellules souches musculaires au stress génotoxique. Ces résultats pourraient avoir des implications dans l'amélioration des thérapies cellulaires de la dysfonction musculaire en agissant sur les régulateurs nouvellement découverts.
DNA double-strand breaks (DSBs) are dangerous DNA damages and a risk factor for genome stability. The maintenance of genome integrity is crucial for adult stem cells that are responsible for regeneration of damaged tissues and tissue homeostasis throughout life. Muscle regeneration in the adult relies on muscle stem cells (satellite cells, SCs) that have a remarkable DSB repair activity, but the underlying mechanism is not known. The aims of the present PhD project were to investigate how muscle differentiation is affected when DSB repair is impaired, and which are the mechanism(s) and the consequences on muscle regeneration. During this study, a novel possibility has arisen, namely that DSB repair factors affects myogenesis independently of their DNA repair activity, suggesting a novel function, not previously anticipated, of…
Advisors/Committee Members: Ricchetti, Miria (thesis director).
Subjects/Keywords: Réparation des cassures double-brin de l’ADN; Cellules souches musculaires; Myogenèse; Kinase DNA-PK; Kinase AKT; Kinase ATM; DNA double strand break repair; Muscle stem cells; Myogenesis; DNAPK kinase; AKT kinase; ATM kinase; 571.6
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Sutcu, H. (2018). Implication of DNA damage and repair in viability and differentiation of muscle stem cells : Implication des dommages à l’ADN et leur réparation sur la viabilité et la différentiation des cellules souches musculaires. (Doctoral Dissertation). Sorbonne université. Retrieved from http://www.theses.fr/2018SORUS125
Chicago Manual of Style (16th Edition):
Sutcu, Haser. “Implication of DNA damage and repair in viability and differentiation of muscle stem cells : Implication des dommages à l’ADN et leur réparation sur la viabilité et la différentiation des cellules souches musculaires.” 2018. Doctoral Dissertation, Sorbonne université. Accessed April 17, 2021.
http://www.theses.fr/2018SORUS125.
MLA Handbook (7th Edition):
Sutcu, Haser. “Implication of DNA damage and repair in viability and differentiation of muscle stem cells : Implication des dommages à l’ADN et leur réparation sur la viabilité et la différentiation des cellules souches musculaires.” 2018. Web. 17 Apr 2021.
Vancouver:
Sutcu H. Implication of DNA damage and repair in viability and differentiation of muscle stem cells : Implication des dommages à l’ADN et leur réparation sur la viabilité et la différentiation des cellules souches musculaires. [Internet] [Doctoral dissertation]. Sorbonne université; 2018. [cited 2021 Apr 17].
Available from: http://www.theses.fr/2018SORUS125.
Council of Science Editors:
Sutcu H. Implication of DNA damage and repair in viability and differentiation of muscle stem cells : Implication des dommages à l’ADN et leur réparation sur la viabilité et la différentiation des cellules souches musculaires. [Doctoral Dissertation]. Sorbonne université; 2018. Available from: http://www.theses.fr/2018SORUS125
Wright State University
18.
Lehman, Jason Alexander.
Novel Redox and DNA-Dependent Conformational Changes in
Human Ku, a DNA-Double Strand Break Repair Protein.
Degree: PhD, Biomedical Sciences PhD, 2008, Wright State University
URL: http://rave.ohiolink.edu/etdc/view?acc_num=wright1211323245
► Ionizing radiation (IR) and radiomimetic drugs used in cancer chemotherapy cause DNA double-strand breaks which are repaired by the nonhomologous end joining (NHEJ) pathway.…
(more)
▼ Ionizing radiation (IR) and radiomimetic
drugs used in cancer chemotherapy cause
DNA double-strand breaks
which are repaired by the nonhomologous end joining (NHEJ) pathway.
Ku is a heterodimeric protein comprised of 70 and 80 kDa subunits
and recognizes free
DNA ends. Once Ku is bound to
DNA, it binds to
the
DNA-dependent protein kinase catalytic subunit (
DNA-PKcs), and
forms a heterotrimeric
DNA-
PK complex for repair and damage
signaling. We have analyzed the Ku protein using
multiple biochemical techniques and uncovered a novel reversible
redox change (Andrews, Lehman and Turchi, (2006) JBC
281(19):13596-603). From this data, we hypothesized that a
redox-dependent conformational change was responsible for the
unexplained differences in our
DNA binding assays. This was
confirmed by limited proteolysis and mass spectrometry analysis of
oxidized and reduced Ku. The conformational change was manifested
by alterations in the Ku70 subunit in proximity to the
DNA binding
site. Our results suggest a model for a Ku-
DNA interaction that is
altered by redox status upon
DNA damage in the cell.
In order to understand the complex structure of
DNA-
PK, we have initially examined Ku-
DNA interactions using
advanced biochemical techniques. Structural studies on Ku by other
groups have utilized truncated versions missing disordered
C-terminal domains (CTDs) from both subunits. Chemical modification
with NHS-biotin and mass spectrometry were used to identify
biotinylated reactive lysines. Biotinylation of free Ku revealed
several lysines on Ku which were reduced or eliminated upon
DNA
binding. Interestingly, in the predicted C-terminal SAP domain of
Ku70, biotinylation patterns suggest a structural change at this
site induced by
DNA binding. Limited proteolytic digests of free
and
DNA-bound Ku revealed a series of unique peptides correlating
to a change in the accessibility of the Ku70 and Ku80 CTDs. A 10
kDa peptide was also identified which was preferentially generated
under non-
DNA-bound conditions and mapped to the Ku70 CTD. These
results indicate a
DNA-dependent movement or structural change in
the CTDs of Ku70 and Ku80 that may contribute to
DNA-PKcs binding
and activation. This is the first demonstration of
DNA-dependent
conformational changes in Ku and will aid in discerning the
mechanism of
DNA-
PK activation.
Advisors/Committee Members: Turchi, John (Advisor), McDougal, James (Committee Chair).
Subjects/Keywords: Biochemistry; DNA repair; Ku; DNA-PK; non-homologous end joining; mass spectrometry; conformational changes; redox
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Lehman, J. A. (2008). Novel Redox and DNA-Dependent Conformational Changes in
Human Ku, a DNA-Double Strand Break Repair Protein. (Doctoral Dissertation). Wright State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=wright1211323245
Chicago Manual of Style (16th Edition):
Lehman, Jason Alexander. “Novel Redox and DNA-Dependent Conformational Changes in
Human Ku, a DNA-Double Strand Break Repair Protein.” 2008. Doctoral Dissertation, Wright State University. Accessed April 17, 2021.
http://rave.ohiolink.edu/etdc/view?acc_num=wright1211323245.
MLA Handbook (7th Edition):
Lehman, Jason Alexander. “Novel Redox and DNA-Dependent Conformational Changes in
Human Ku, a DNA-Double Strand Break Repair Protein.” 2008. Web. 17 Apr 2021.
Vancouver:
Lehman JA. Novel Redox and DNA-Dependent Conformational Changes in
Human Ku, a DNA-Double Strand Break Repair Protein. [Internet] [Doctoral dissertation]. Wright State University; 2008. [cited 2021 Apr 17].
Available from: http://rave.ohiolink.edu/etdc/view?acc_num=wright1211323245.
Council of Science Editors:
Lehman JA. Novel Redox and DNA-Dependent Conformational Changes in
Human Ku, a DNA-Double Strand Break Repair Protein. [Doctoral Dissertation]. Wright State University; 2008. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=wright1211323245
East Carolina University
19.
Rushing, Amanda Williams.
Human T-Cell Leukemia Virus Type I Basic Leucine Zipper Factor (HBZ) Modulates Cellular DNA Damage Repair and Antioxidant Responses to Promote Host Cell Survival and Leukemogenesis.
Degree: PhD, PHD-Microbiology & Immunology, 2018, East Carolina University
URL: http://hdl.handle.net/10342/6782
► Approximately twenty million people worldwide are infected with Human T-cell Leukemia Virus type 1 (HTLV-1). HTLV-1 establishes a life-long, chronic infection which can result in…
(more)
▼ Approximately twenty million people worldwide are infected with Human T-cell Leukemia Virus type 1 (HTLV-1). HTLV-1 establishes a life-long, chronic infection which can result in the development of severe HTLV-1 associated diseases: Adult T-cell Leukemia (ATL) or HTLV-1-associated myelopathy/ tropical spastic paraparesis (HAM/TSP). ATL is a fatally-aggressive lymphoproliferative disorder of HTLV-1-infected CD4+ T-cells. HAM/TSP is a debilitating neurodegenerative disorder that greatly reduces quality of life. There exists a distinct lack of effective vaccine and therapeutic options for both ATL and HAM/TSP patients. Though the mechanisms that drive HTLV-1 pathogenesis remain poorly understood, extensive study of the virus has revealed the importance of two viral regulatory proteins in disease progression: Tax and HBZ. Tax is a transcriptional regulator which is important for establishing initial infection; however, Tax is highly immunogenic and stimulates a robust antiviral immune response. To evade immune detection, HTLV-1 host cells often silence Tax expression through the transcriptionally repressive activity of the basic leucine zipper factor HBZ. HBZ is expressed throughout all phases of infection and plays important roles in maintaining host cell survival and clonal expansion. HBZ expression is sufficient to induce ATL-like disease progression in in vivo models, supporting its contribution to leukemogenesis in patients. Here, we report novel functions of HBZ that may promote the long-term survival of infected lymphocytes, including the direct upregulation of antioxidant response gene expression, the detoxification of reactive oxygen species, and the prevention of oxidative stress-induced cell death. We also evaluated the contribution of HBZ to the accumulation of genetic abnormalities which may promote leukemogenesis. Here, we report that HBZ contributes to genetic instability by affecting the double-stranded
DNA damage repair system non-homologous end joining (NHEJ), possibly through specific interactions with
DNA repair proteins. These findings support the role of HBZ in promoting leukemogenesis through the accumulation of chromosomal abnormalities which arise from double-stranded
DNA breaks. Together, the data presented here indicate that HBZ is an important driving force in the prolonged survival and transformation of HTLV-1-infected lymphocytes.
Advisors/Committee Members: Lemasson, Isabelle (advisor).
Subjects/Keywords: HBZ; leukemogenesis; NHEJ; Ku70; Ku80; DNA-PK; HMOX-1; small Maf; antioxidant; oxidative stress; Human T-lymphotropic virus 1; Cell Survival; Leucine Zippers; Leukemia, T-Cell; DNA Damage; Gene Products, tax
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Rushing, A. W. (2018). Human T-Cell Leukemia Virus Type I Basic Leucine Zipper Factor (HBZ) Modulates Cellular DNA Damage Repair and Antioxidant Responses to Promote Host Cell Survival and Leukemogenesis. (Doctoral Dissertation). East Carolina University. Retrieved from http://hdl.handle.net/10342/6782
Chicago Manual of Style (16th Edition):
Rushing, Amanda Williams. “Human T-Cell Leukemia Virus Type I Basic Leucine Zipper Factor (HBZ) Modulates Cellular DNA Damage Repair and Antioxidant Responses to Promote Host Cell Survival and Leukemogenesis.” 2018. Doctoral Dissertation, East Carolina University. Accessed April 17, 2021.
http://hdl.handle.net/10342/6782.
MLA Handbook (7th Edition):
Rushing, Amanda Williams. “Human T-Cell Leukemia Virus Type I Basic Leucine Zipper Factor (HBZ) Modulates Cellular DNA Damage Repair and Antioxidant Responses to Promote Host Cell Survival and Leukemogenesis.” 2018. Web. 17 Apr 2021.
Vancouver:
Rushing AW. Human T-Cell Leukemia Virus Type I Basic Leucine Zipper Factor (HBZ) Modulates Cellular DNA Damage Repair and Antioxidant Responses to Promote Host Cell Survival and Leukemogenesis. [Internet] [Doctoral dissertation]. East Carolina University; 2018. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/10342/6782.
Council of Science Editors:
Rushing AW. Human T-Cell Leukemia Virus Type I Basic Leucine Zipper Factor (HBZ) Modulates Cellular DNA Damage Repair and Antioxidant Responses to Promote Host Cell Survival and Leukemogenesis. [Doctoral Dissertation]. East Carolina University; 2018. Available from: http://hdl.handle.net/10342/6782
University of Gothenburg / Göteborgs Universitet
20.
[No author].
Repair of DNA double-stranded breaks in human cells.
Degree: 2005, University of Gothenburg / Göteborgs Universitet
URL: http://hdl.handle.net/2077/16596
► DNA is continuously subjected to degradation. Therefore, our cells need to constantly repair its DNA to prevent mutations and in the long run cancer. In…
(more)
▼ DNA is continuously subjected to degradation. Therefore, our cells need to constantly repair its DNA to prevent mutations and in the long run cancer. In mammalian cells, when DNA is broken right off, a double-stranded break (DSB) is produced, and the ends are ligated by a process called non-homologous end-joining (NHEJ). NHEJ involves a protein kinase, DNA-PK that binds and becomes activated by the DNA ends. DNA-PK is composed of the DNA-binding subunit Ku and the catalytic subunit DNA-PKcs. The overall aim of the present investigation was to take a closer look at the repair of DSBs in human cells and the involvement of the DNA-PK in this process. Using purified enzymes and kinase assays, we studied the activation of DNA-PK by different forms of broken DNA ends. DNA-PK was activated by DNA-ends containing a wide variety of modifications. This indicated that DSBs that remain undetected by DNA-PK are rare. The only exception was DSBs generated by the cancer drug etoposide. In this case the DSB is covered by topoisomerase II and can therefore not be recognized by DNA-PK.We also studied DNA-PK activation by DNA strand breaks generated by agents used in cancer treatment. DSBs produced by bleomycin, calicheamicin gamma1, and different kinds of radiation activated DNA-PK to maximal levels. We also compared the cleavage of cellular DNA and purified plasmid DNA by calicheamicin gamma1 (CLM), a drug used in cancer treatment. Our findings show that the ratio of DNA DSBs to single-stranded breaks (SSB) in cellular DNA was 1:3, close to the 1:2 ratio observed when CLM cleaved purified plasmid DNA. CLM-induced DSBs were repaired slowly but completely and resulted in a normal and strong DSB-response in cells. The high DSB/SSB ratio, specificity for DNA and the even damage distribution makes CLM a superior drug for studies of the DSB-response. Finally, we identified and characterized a DNA-PK-inhibitor, SU11752. SU11752 was a potent and selective inhibitor of DNA-PK. Results showed that SU11752 inhibited DNA-PK by ATP competition and sensitized cells 5-fold to ionizing radiation (IR) by inhibition of DSB repair. SU11752 defines a new class of drugs that serves as a starting point for development of specific DNA-PK inhibitors. Loss of DNA-PK results in increased sensitivity to IR due to inefficient repair of DNA DSBs. Over-expression of DNA-PK in tumor cells conversely results in resistance to IR, because DSBs are repaired quickly. It is therefore possible that inhibition of DNA-PK will enhance the preferential killing of tumor cells by radiotherapy.
Subjects/Keywords: DNA-PK; DNA double-stranded break; DSB; DNA single-stranded break; SSB; DNA damage; ionizing radiation; IR; DNA repair; calicheamicin gamma1; bleomycin; etoposide; topoisomerase II; radiotherapy; radiosensitizer; ATM
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
author], [. (2005). Repair of DNA double-stranded breaks in human cells. (Thesis). University of Gothenburg / Göteborgs Universitet. Retrieved from http://hdl.handle.net/2077/16596
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
author], [No. “Repair of DNA double-stranded breaks in human cells.” 2005. Thesis, University of Gothenburg / Göteborgs Universitet. Accessed April 17, 2021.
http://hdl.handle.net/2077/16596.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
author], [No. “Repair of DNA double-stranded breaks in human cells.” 2005. Web. 17 Apr 2021.
Vancouver:
author] [. Repair of DNA double-stranded breaks in human cells. [Internet] [Thesis]. University of Gothenburg / Göteborgs Universitet; 2005. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/2077/16596.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
author] [. Repair of DNA double-stranded breaks in human cells. [Thesis]. University of Gothenburg / Göteborgs Universitet; 2005. Available from: http://hdl.handle.net/2077/16596
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Gothenburg / Göteborgs Universitet
21.
Ismail, Ismail Hassan 1975-.
Recognition and signaling of DNA double-strand breaks in human cells.
Degree: 2006, University of Gothenburg / Göteborgs Universitet
URL: http://hdl.handle.net/2077/16855
► DNA double-strand breaks (DSBs) are the most toxic type of DNA damage. Fortunately, our cells have highly conserved pathways that detect and repair DSBs. Defects…
(more)
▼ DNA double-strand breaks (DSBs) are the most toxic type of DNA damage. Fortunately, our cells have highly conserved pathways that detect and repair DSBs. Defects in DSB signaling and DSB repair pathways result in genomic instability that predisposes for cancer development. In mammalian cells DSBs signaling involves ATM (ataxia telangiectasia mutated) and DNA-dependent protein kinase (DNA-PK). However, it remains unclear how these enzymes recognize DNA damage and transmit the signal to downstream effectors. The overall aim of the present study was to study DSB signaling and try to use this knowledge to enhance cancer treatment.To validate the application of the enediyne calicheamicin kappa1 (CLM) in DSB studies, we characterized the cleavage of cellular DNA by CLM. We found that CLM specifically targets DNA without interference from proteins or RNA. The DSBs/SSBs ratio in cellular DNA was 1:3, close to the 1:2 ratio observed when CLM cleaved purified plasmid. CLM-induced DSBs were repaired slowly but completely and resulted in a strong DSB response. The high DSBs/SSBs ratio and specificity for DNA makes CLM a superior drug for DSB response studies.We then used CLM together with other agents that produce different number of DSBs and SSBs in cells, to test if ATM was specifically activated by IR-induced DSBs. We found that ATM was not activated at all in response to SSBs. We also found that the number of DSBs induced by different drugs and radiation correlates closely with the ATM activation, whereas no correlation was found with the number of SSBs. Our data indicate that ATM is directly activated by the few DSBs that are introduced by IR.An early event after introduction of DSBs is the phosphorylation of histone H2AX on serine 139 (HAXS139ph). We have developed a flow cytometry-based method optimized for measuring H2AXS139ph in blood cells. We found that all nucleated blood cells are able to phosphorylate H2AX in response to DSBs, but to different levels. There was a pronounced interindividual difference in the H2AXS139ph signal at a given DSB level, indicating that there is an inherent difference in the DSB response among individuals. This method could be used to monitor patients undergoing chemotherapy or to examine variation in response to treatment among cancer patients.In an effort to develop a specific DNA-PK-inhibitor, we have characterized SU11752. Our data showed that SU11752 inhibited DNA-PK by competitive inhibition of ATP-binding. SU11752 inhibited DSB repair and sensitizes cells 5-fold to IR. At concentrations that inhibited DSB repair, cell cycle progression was normal, and ATM kinase activity was not inhibited. Taken together, our data indicate that SU11752 is a selective DNA-PK inhibitor and defines a new class of drugs that may serve as a starting point for the development of specific DNA-PK inhibitors.
Subjects/Keywords: DNA-PK; DNA double-strand break; DSB; DNA single-strand break; SSB; DNA damage; ionizing radiation; IR; DNA repair; calicheamicin kappa1; ATM; hydrogen peroxide; H2AX; radiotherapy; radiosensitizer; flow cytometry
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Ismail, I. H. 1. (2006). Recognition and signaling of DNA double-strand breaks in human cells. (Thesis). University of Gothenburg / Göteborgs Universitet. Retrieved from http://hdl.handle.net/2077/16855
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Ismail, Ismail Hassan 1975-. “Recognition and signaling of DNA double-strand breaks in human cells.” 2006. Thesis, University of Gothenburg / Göteborgs Universitet. Accessed April 17, 2021.
http://hdl.handle.net/2077/16855.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Ismail, Ismail Hassan 1975-. “Recognition and signaling of DNA double-strand breaks in human cells.” 2006. Web. 17 Apr 2021.
Vancouver:
Ismail IH1. Recognition and signaling of DNA double-strand breaks in human cells. [Internet] [Thesis]. University of Gothenburg / Göteborgs Universitet; 2006. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/2077/16855.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Ismail IH1. Recognition and signaling of DNA double-strand breaks in human cells. [Thesis]. University of Gothenburg / Göteborgs Universitet; 2006. Available from: http://hdl.handle.net/2077/16855
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Gothenburg / Göteborgs Universitet
22.
Björk-Eriksson, Thomas 1960-.
Potential biological markers of tumour response to radiation therapy in head and neck cancers.
Degree: 1999, University of Gothenburg / Göteborgs Universitet
URL: http://hdl.handle.net/2077/15273
► The rationale behind studying biological markers of tumour response to radiation therapy in head and neck cancers is to increase the individualisation of radiation therapy.…
(more)
▼ The rationale behind studying biological markers of tumour response to radiation therapy in head and neck cancers is to increase the individualisation of radiation therapy. This should ultimately lead to improvements in local control and survival and reduced morbidity. An evaluation was made of the theoretical and practical value of using low-dose rate irradiation to increase the resolution of clonogenic assays for radiosensitivity testing. In tumour cell lines low-dose rate irradiation improved discrimination between tumour radioresponsiveness groups. However, low-dose rate irradiation of primary human tumours followed by soft-agar clonogenic assay was impractical because it reduced the success rate for obtaining radiosensitivity data.One hundred and forty specimens of malignant head and neck tumours of different histology types were assessed for ability to grow in vitro (colony forming efficiency, CFE) and inherent tumour radiosensitivity (surviving fraction at 2 Gy, SF2) using a clonogenic soft-agar assay. The success rate for growing colonies was 74% (104/140) with a median CFE = 0.031%. SF2 was obtained for 88/140 patients (63%) with a median SF2 = 0.43. A comparison was made of SF2 values for different primary human tumour types. This showed that head and neck- (p = 0.03), cervix- (p = 0.02) and colorectal carcinomas (p = 0.003) were significantly more radioresistant than lymphomas. The relationships between proliferation, TP53 and SF2 were evaluated. No correlations were seen between SF2 and any of the parameters analysed. The study demonstrated the feasibility of obtaining parallel measurements of different biological markers in a large number of patients with head and neck cancers.A study was made of SF2 in relation to the immunohistochemical expression levels of the individual components (Ku (p70/p80) and DNA-PKcs) of the DNA double strand break repair enzyme, DNA-PK. No significant relationship was found between SF2 and the expression levels of Ku (p70/p80) or DNA-PKcs for patients with head and neck cancers.Finally, the relationship between SF2 and treatment outcome was prospectively studied in 84 patients with malignant head and neck cancers. SF2 was found to be a significant prognostic factor for local control (p = 0.036).
Subjects/Keywords: Predictive assay; inherent radiosensitivity; SF2; proliferation; Tpot; TP53; DNA-PK; Ku; head and neck cancer
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Björk-Eriksson, T. 1. (1999). Potential biological markers of tumour response to radiation therapy in head and neck cancers. (Thesis). University of Gothenburg / Göteborgs Universitet. Retrieved from http://hdl.handle.net/2077/15273
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Björk-Eriksson, Thomas 1960-. “Potential biological markers of tumour response to radiation therapy in head and neck cancers.” 1999. Thesis, University of Gothenburg / Göteborgs Universitet. Accessed April 17, 2021.
http://hdl.handle.net/2077/15273.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Björk-Eriksson, Thomas 1960-. “Potential biological markers of tumour response to radiation therapy in head and neck cancers.” 1999. Web. 17 Apr 2021.
Vancouver:
Björk-Eriksson T1. Potential biological markers of tumour response to radiation therapy in head and neck cancers. [Internet] [Thesis]. University of Gothenburg / Göteborgs Universitet; 1999. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/2077/15273.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Björk-Eriksson T1. Potential biological markers of tumour response to radiation therapy in head and neck cancers. [Thesis]. University of Gothenburg / Göteborgs Universitet; 1999. Available from: http://hdl.handle.net/2077/15273
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Minnesota
23.
Fattah, Farjana Jahan.
The impact of loss of function mutations of NHEJ genes on gene targeting and DNA DSB repair in human somatic cells.
Degree: PhD, Biochemistry, Molecular Biology, and Biophysics, 2009, University of Minnesota
URL: http://purl.umn.edu/50889
► Non-homologous end-joining (NHEJ) is the predominant repair pathway for DNA double-strand breaks (DSBs) in human cells. The core NHEJ pathway is composed of seven factors:…
(more)
▼ Non-homologous end-joining (NHEJ) is the predominant repair pathway for DNA double-strand breaks (DSBs) in human cells. The core NHEJ pathway is composed of seven factors: Ku70, Ku86, DNA-PKcs, Artemis, XRCC4, XLF and LIGIV. Mutation of any one of these NHEJ genes leads either to death, profound immune deficiencies, ionizing radiation sensitivity and/or cancer predisposition in human patients. We attempted to generate Ku70-null human somatic cells using a rAAV-based gene knockout strategy. Our data demonstrated that Ku70 is an essential gene in human somatic cells. More importantly, however, in Ku70+/- cells, the frequency of gene targeting was 5- to 10-fold higher than in wild type cells. RNA interference and short-hairpinned RNA strategies to deplete Ku70 phenocopied these results in wild-type cells and greatly accentuated them in Ku70+/- cell lines. Thus, Ku70 protein levels significantly influenced the frequency of rAAV-mediated gene targeting in human somatic cells.
XLF is the newly identified core factor for NHEJ. To characterize XLF function in human cells, we knocked out XLF gene in HCT116 cells. XLF deficient cells are highly sensitive to ionizing radiation and DNA damaging agent, and have intrinsic DNA DSB repair defects. In V(D)J recombination assay, we find that XLF deficient cells have dramatic defect to form both V(D)J coding and signal joints. The phenotypes of XLF deficiency were rescued by a WT XLF cDNA over-expression. We conclude that, in humans, XLF is essential for C-NHEJ mediated repair of DNA-DSBs.
Biochemical and genetic studies in mouse and hamster cells showed that DNA ends can also be joined via a backup pathway, especially when proteins responsible for NHEJ, are reduced or absent. In order to get insights in to backup NHEJ mechanism, we employed a reporter system based on the in vivo rejoining of cohesive and incompatible ends. We report here more than 10 to 20 fold reduction in NHEJ proficiency in DNA-PKcs, XLF and LIGIV null human cells, which is characterized by an increase in microhomology use. Strikingly, conditional knock-out of Ku86 did not result in defect in end-joining, while having an impact on repair fidelity.
Subjects/Keywords: DNA-PK; Gene Targeting; Ku86/Ku70; Non-Homologous End Joining; Biochemistry, Molecular Biology, and Biophysics
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Fattah, F. J. (2009). The impact of loss of function mutations of NHEJ genes on gene targeting and DNA DSB repair in human somatic cells. (Doctoral Dissertation). University of Minnesota. Retrieved from http://purl.umn.edu/50889
Chicago Manual of Style (16th Edition):
Fattah, Farjana Jahan. “The impact of loss of function mutations of NHEJ genes on gene targeting and DNA DSB repair in human somatic cells.” 2009. Doctoral Dissertation, University of Minnesota. Accessed April 17, 2021.
http://purl.umn.edu/50889.
MLA Handbook (7th Edition):
Fattah, Farjana Jahan. “The impact of loss of function mutations of NHEJ genes on gene targeting and DNA DSB repair in human somatic cells.” 2009. Web. 17 Apr 2021.
Vancouver:
Fattah FJ. The impact of loss of function mutations of NHEJ genes on gene targeting and DNA DSB repair in human somatic cells. [Internet] [Doctoral dissertation]. University of Minnesota; 2009. [cited 2021 Apr 17].
Available from: http://purl.umn.edu/50889.
Council of Science Editors:
Fattah FJ. The impact of loss of function mutations of NHEJ genes on gene targeting and DNA DSB repair in human somatic cells. [Doctoral Dissertation]. University of Minnesota; 2009. Available from: http://purl.umn.edu/50889
Université de Sherbrooke
24.
Roy, Evelyne.
Modulation de la réponse inflammatoire intestinale par la kinase DNA-PK.
Degree: 2007, Université de Sherbrooke
URL: http://savoirs.usherbrooke.ca/handle/11143/3931
► Des résultats obtenus antérieurement au laboratoire ont démontré l'induction des facteurs de transcription C/EBPs par l'IL-1? ainsi que leur implication dans la régulation de la…
(more)
▼ Des résultats obtenus antérieurement au laboratoire ont démontré l'induction des facteurs de transcription C/EBPs par l'IL-1? ainsi que leur implication dans la régulation de la transcription de gènes de réponse inflammatoire telle que l'haptoglobine au niveau de la cellule épithéliale intestinale. En outre, il a déjà été démontré que la phosphoiylation des C/EBPs peut moduler leur activité et des études au laboratoire ont démontré l'interaction in vitro entre l'isoforme C/EBP? et la kinase
DNA-
PK. Par l'utilisation de l'inhibiteur non spécifique de la famille PI(3)K, la wortmannine, il a été observé que la
DNA-
PK phosphoryle C/EBP?. La
DNA-
PK est une kinase qui répare les bris d'ADN double brin en participant au processus de jonction des extrémités non-homologues. Ainsi, nous avons étudié la modulation de la réponse inflammatoire intestinale par la
DNA-
PK, en s'attardant plus particulièrement à deux familles de facteurs de transcription, soit NF-?B et les C/EBPs. Par l'utilisation d'un inhibiteur sélectif de la
DNA-
PK, le IC60211, la phosphorylation in vitro de la région N-terminale de C/EBP? par la
DNA-
PK a d'abord été confirmé. Puisque la
DNA-
PK est activée par les bris d'ADN double brin, la doxorubicine, un agent génotoxique, a été utilisé pour la suite du projet. Nous avons montré que la doxorubicine engendre une hausse de la capacité de liaison à l'ADN de NF-?B induite par l'IL-1? et que les complexes formés comprenaient surtout la sousunité p65. Ceci s'accompagne d'une hausse des niveaux nucléaires de p65 ainsi que d'une baisse d'expression de l'inhibiteur cytoplasmique de NF-?B, I?B?. Par contre, par l'utilisation de l'inhibiteur sélectif de la
DNA-
PK, le NU7026, nos résultats suggèrent que ces effets sont
DNA-
PK indépendants. En effet, un rétablissement de la capacité de liaison à l'ADN de NF-?B n'est pas observé lors d'une préincubation avec cet inhibiteur avant de traiter à la doxorubicine puis à l'IL-1?. En ce qui concerne les C/EBPs, nos résultats démontrent que la doxorubicine diminue l'activité transcriptionnelle de l'isoforme C/EBP? sur le promoteur du gène haptoglobine. Alors qu'un traitement à l'IL-1? induit une augmentation de la liaison des C/EBPs à HaptoA, nos résultats montrent qu'un pré-traitement à la doxorubicine empêche cette induction. De plus, les niveaux protéiques de C/EBP? et C/EBP? induits par l'IL-1? sont abaissés par la doxorubicine. Également, les niveaux d'ARNm de C/EBP? induits par l'IL-1 p et de deux de ses gènes cibles inflammatoires, l'haptoglobine et lipocalin2, sont diminués par un prétraitement à la doxorubicine. Par l'utilisation du NU7026, nous démontrons un rétablissement partiel de la capacité de liaison à l'ADN de C/EB13? et de C/EBP? qui était réduite par un traitement à la doxorubicine, à des niveaux comparables à la condition sans traitement et à la condition IL-1?, respectivement. Cependant, cet inhibiteur permet le rétablissement des niveaux de protéine et d'ARNm de C/EBP? (induits par l'IL-1?) qui étaient réprimés par un prétraitement à la doxorubicine mais non…
Advisors/Committee Members: Asselin, Claude (advisor).
Subjects/Keywords: Facteur de transcription C/EBP; Facteur de transcription NF-kB; DNA-PK; Réponse inflammatoire intestinale; Haptoglobine
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Roy, E. (2007). Modulation de la réponse inflammatoire intestinale par la kinase DNA-PK. (Masters Thesis). Université de Sherbrooke. Retrieved from http://savoirs.usherbrooke.ca/handle/11143/3931
Chicago Manual of Style (16th Edition):
Roy, Evelyne. “Modulation de la réponse inflammatoire intestinale par la kinase DNA-PK.” 2007. Masters Thesis, Université de Sherbrooke. Accessed April 17, 2021.
http://savoirs.usherbrooke.ca/handle/11143/3931.
MLA Handbook (7th Edition):
Roy, Evelyne. “Modulation de la réponse inflammatoire intestinale par la kinase DNA-PK.” 2007. Web. 17 Apr 2021.
Vancouver:
Roy E. Modulation de la réponse inflammatoire intestinale par la kinase DNA-PK. [Internet] [Masters thesis]. Université de Sherbrooke; 2007. [cited 2021 Apr 17].
Available from: http://savoirs.usherbrooke.ca/handle/11143/3931.
Council of Science Editors:
Roy E. Modulation de la réponse inflammatoire intestinale par la kinase DNA-PK. [Masters Thesis]. Université de Sherbrooke; 2007. Available from: http://savoirs.usherbrooke.ca/handle/11143/3931
25.
Woods, Derek S.
The influence of the Ku80 carboxy-terminus on activation of the DNA-dependent protein kinase and DNA repair is dependent on the structure of DNA cofactors.
Degree: 2014, IUPUI
URL: http://hdl.handle.net/1805/4665
► Indiana University-Purdue University Indianapolis (IUPUI)
In mammalian cells DNA double strand breaks (DSBs) are highly variable with respect to sequence and structure all of which…
(more)
▼ Indiana University-Purdue University Indianapolis (IUPUI)
In mammalian cells DNA double strand breaks (DSBs) are highly variable with respect to sequence and structure all of which are recognized by the DNA- dependent protein kinase (DNA-PK), a critical component for the resolution of these breaks. Previously studies have shown that DNA-PK does not respond the same way to all DSBs but how DNA-PK senses differences in DNA substrate sequence and structure is unknown. Here we explore the enzymatic mechanism by which DNA-PK is activated by various DNA substrates. We provide evidence that recognition of DNA structural variations occur through distinct protein-protein interactions between the carboxy terminal (C-terminal) region of Ku80 and DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Discrimination of terminal DNA sequences, on the other hand, occurs independently of Ku 80 C-terminal interactions and results exclusively from DNA-PKcs interactions with the DNA. We also show that sequence differences in DNA termini can drastically influence DNA repair through altered DNA-PK activation. Our results indicate that even subtle differences in DNA substrates influence DNA-PK activation and ultimately Non-homologous End Joining (NHEJ) efficiency.
Advisors/Committee Members: Turchi, John J., Harrington, Maureen A., Malkova, Anna L., Takagi, Yuichiro.
Subjects/Keywords: DNA Repair,; NHEJ; DNA-PK; Ku70/80; Ku80 Carboxy Terminus; DNA – Research – Methodology; DNA-protein interactions; Protein-protein interactions; DNA – Synthesis; Enzymes – Analysis; Protein kinases – Research – Evaluation; DNA repair; DNA damage; DNA-binding proteins; Cellular control mechanisms; Nucleotide sequence; Mutagenesis; Biochemical genetics
…NHEJ requires the formation and activation of the DNA-dependent
protein kinase (DNA-PK… …x29;. Once activated, DNA-PK functions to regulate NHEJ pathway
progression as well as… …addition to its direct role in NHEJ, recent work has
demonstrated that DNA-PK also regulates HR… …DNA termini. DNA-PKcs is
recruited to form the DNA-PK heterotrimer. DNA-PK undergoes… …autophosphorylation as
well as phosphorylation of downstream molecules. DNA termini are processed and
DNA-PK…
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Woods, D. S. (2014). The influence of the Ku80 carboxy-terminus on activation of the DNA-dependent protein kinase and DNA repair is dependent on the structure of DNA cofactors. (Thesis). IUPUI. Retrieved from http://hdl.handle.net/1805/4665
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Woods, Derek S. “The influence of the Ku80 carboxy-terminus on activation of the DNA-dependent protein kinase and DNA repair is dependent on the structure of DNA cofactors.” 2014. Thesis, IUPUI. Accessed April 17, 2021.
http://hdl.handle.net/1805/4665.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Woods, Derek S. “The influence of the Ku80 carboxy-terminus on activation of the DNA-dependent protein kinase and DNA repair is dependent on the structure of DNA cofactors.” 2014. Web. 17 Apr 2021.
Vancouver:
Woods DS. The influence of the Ku80 carboxy-terminus on activation of the DNA-dependent protein kinase and DNA repair is dependent on the structure of DNA cofactors. [Internet] [Thesis]. IUPUI; 2014. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/1805/4665.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Woods DS. The influence of the Ku80 carboxy-terminus on activation of the DNA-dependent protein kinase and DNA repair is dependent on the structure of DNA cofactors. [Thesis]. IUPUI; 2014. Available from: http://hdl.handle.net/1805/4665
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
. 
Open Access Theses and Dissertations
