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You searched for subject:(ADNmt). Showing records 1 – 2 of 2 total matches.

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Universitat Autònoma de Barcelona

1. Blázquez Bermejo, Cora. Estimulación de la síntesis de nucleótidos como tratamiento de los defectos en la replicación del ADN mitocondrial.

Degree: Departament de Bioquímica i Biologia Molecular, 2019, Universitat Autònoma de Barcelona

The mitochondrial DNA depletion and multiple deletions syndrome (mtDNA) (MDDS) comprises a group of rare diseases of autosomal recessive or dominant inheritance, due to alterations in the maintenance of mtDNA. These alterations manifest as a loss of mtDNA molecules (depletion), accumulation of multiple deletions or point mutations in the mtDNA. The clinical spectrum of MDDS is very broad and heterogeneous. It can manifest in a wide range of phenotypes with different severity, from simple and relatively mild affectations to rapidly progressing and\/or multiorgan diseases that lead to early death of the patient during his first years of life. Genetically, the MDDS is also very heterogeneous, being associated with mutations in nuclear genes whose products are somehow involved in processes related with mtDNA maintenance. One of these processes is dNTP homeostasis, which is essential to sustain a correct replication of mtDNA. This doctoral thesis work consists of in vitro and in vivo preclinical studies on the administration of deoxyribonucleosides (dNs), precursors for the synthesis of dNTPs, as a therapy for treating two forms of MDDS, the deficiencies in thymidine kinase 2 (TK2) and in the catalytic subunit of mitochondrial polymerase (POLG). TK2 is the kinase responsible for the first and limiting phosphorylation of deoxythymidine (dThd) and deoxycytidine (dCtd) in mitochondria, which is essential to obtain dTTP and dCTP. TK2 deficiency usually presents as a severe myopathy associated with a marked depletion of mtDNA in muscle. We have tested the administration of dThd and dCtd in a murine knock-out model for Tk2 (Tk2KO). These mice develop a fatal encephalomyopathy that progresses rapidly leading to death at 16 days of age. With the treatment, survival of Tk2KO mice is extended to 34 days, and the levels of mtDNA in muscle are normalized. However, the therapeutic effect is lost with aging. Here, we describe important changes in dNTP metabolism occurring during normal mouse development and reducing the effectiveness of the treatment with aging. On the other hand, we have worked with fibroblasts derived from patients with mutations in the catalytic subunit of polymerase-gamma (POLG), a protein responsible for mtDNA synthesis. Mutations in this enzyme cause SDDM with a broad clinical spectrum associated with depletion and multiple deletions of mtDNA. The dNs-based treatment induces an increase in the content of the four mitochondrial dNTPs, and this is sufficient to restore the mtDNA replicative capacity while preserving its fidelity, in cells with mutations affecting the different functional domains of POLG. The results obtained in this work suggest that stimulating the dNTP synthesis through dNs supplementation could be a valid therapeutic strategy for MDDS other than TK2 or POLG deficiency, as well as for other diseases in which an increase in mtDNA replication may result beneficial. Advisors/Committee Members: [email protected] (authoremail), true (authoremailshow), Cámara Navarro, Yolanda (director), Martí Seves, Ramon (director), Vila Bover, Miquel (tutor).

Subjects/Keywords: Adnmt; Mtdna; Tk2; Polg; Ciències de la Salut; 57

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Blázquez Bermejo, C. (2019). Estimulación de la síntesis de nucleótidos como tratamiento de los defectos en la replicación del ADN mitocondrial. (Thesis). Universitat Autònoma de Barcelona. Retrieved from http://hdl.handle.net/10803/670111

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):

Blázquez Bermejo, Cora. “Estimulación de la síntesis de nucleótidos como tratamiento de los defectos en la replicación del ADN mitocondrial.” 2019. Thesis, Universitat Autònoma de Barcelona. Accessed January 16, 2021. http://hdl.handle.net/10803/670111.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Blázquez Bermejo, Cora. “Estimulación de la síntesis de nucleótidos como tratamiento de los defectos en la replicación del ADN mitocondrial.” 2019. Web. 16 Jan 2021.

Vancouver:

Blázquez Bermejo C. Estimulación de la síntesis de nucleótidos como tratamiento de los defectos en la replicación del ADN mitocondrial. [Internet] [Thesis]. Universitat Autònoma de Barcelona; 2019. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/10803/670111.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Blázquez Bermejo C. Estimulación de la síntesis de nucleótidos como tratamiento de los defectos en la replicación del ADN mitocondrial. [Thesis]. Universitat Autònoma de Barcelona; 2019. Available from: http://hdl.handle.net/10803/670111

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

2. Chevigny, Nicolas. Caractérisation des fonctions de TRCF et de RADA dans l'expression et la maintenance des génomes des organelles chez Arabidopsis thaliana : Characterization of TRCF and RADA functions in the expression and maintenance of organelle genomes in Arabidopsis thaliana.

Degree: Docteur es, Aspects moléculaires et cellulaires de la biologie, 2019, Université de Strasbourg

La mitochondrie et le chloroplaste possèdent un génome dont l’expression et la maintenance dépendent de facteurs codés par le génome nucléaire. L’ADN mitochondrial des plantes (ADNmt) est caractérisé par d’importantes activités de recombinaison qui modulent sa structure et contribuent à son évolution. Au cours de ma thèse, j’ai caractérisé l’hélicase RADA qui est impliquée dans les étapes tardives de la recombinaison homologue organellaire. RADA possède des fonctions similaires à son homologue bactérien (RadA), mais semble jouer un rôle plus important dans les organelles de plantes. L’expression du génome chloroplastique (ADNcp) repose sur deux types d’ARN polymérases : la NEP, codés par le génome nucléaire et la PEP, codés par l’ADNcp. Durant ma thèse, j’ai également étudié le rôle de TRCF, homologue du facteur Mfd et adressé aux chloroplastes. Chez les bactéries, Mfd est impliqué dans le dégagement des ARN polymérases bloquées par des lésions et le recrutement de facteurs de réparation. Chez Arabidopsis, TRCF n’est plus impliqué dans la réparation, mais semble jouer un rôle dans la régulation de l’expression des gènes chloroplastiques.

The mitochondria and chloroplasts have their own genomes whose expression and maintenance depend on factors encoded by the nuclear genome. The plant mitochondrial DNA (mtDNA) is characterized by important recombination activities that modulate its structure and contribute to its evolution. During my thesis, I characterized the RADA helicase that is involved in the late stages of organelle homologous recombination. RADA has similar functions to its bacterial homolog (RadA), but seems to play a more important role in plant organelles. The expression of the chloroplast genome (cpDNA) relies on two types of RNA polymerases: NEP encoded by the nuclear genome and PEP encoded by the cpDNA. During my thesis, I also studied the role of TRCF, an homolog of the Mfd factor which is addressed to chloroplasts. In bacteria, Mfd is involved in the release of stalled RNA polymerases by lesions and the recruitment of repair factors. In Arabidopsis, TRCF is no longer involved in repair but appears to play a role in the regulation of chloroplast gene expression.

Advisors/Committee Members: Gualberto, José (thesis director).

Subjects/Keywords: ADNmt, recombinaison; Migration de branche; RADA; ADNcp régulation de l’expression; PEP; TRCF; MtDNA, recombination; Branch migration; RADA; CDNA expression regulation; PEP; TRCF; 572.8

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Chevigny, N. (2019). Caractérisation des fonctions de TRCF et de RADA dans l'expression et la maintenance des génomes des organelles chez Arabidopsis thaliana : Characterization of TRCF and RADA functions in the expression and maintenance of organelle genomes in Arabidopsis thaliana. (Doctoral Dissertation). Université de Strasbourg. Retrieved from http://www.theses.fr/2019STRAJ042

Chicago Manual of Style (16th Edition):

Chevigny, Nicolas. “Caractérisation des fonctions de TRCF et de RADA dans l'expression et la maintenance des génomes des organelles chez Arabidopsis thaliana : Characterization of TRCF and RADA functions in the expression and maintenance of organelle genomes in Arabidopsis thaliana.” 2019. Doctoral Dissertation, Université de Strasbourg. Accessed January 16, 2021. http://www.theses.fr/2019STRAJ042.

MLA Handbook (7th Edition):

Chevigny, Nicolas. “Caractérisation des fonctions de TRCF et de RADA dans l'expression et la maintenance des génomes des organelles chez Arabidopsis thaliana : Characterization of TRCF and RADA functions in the expression and maintenance of organelle genomes in Arabidopsis thaliana.” 2019. Web. 16 Jan 2021.

Vancouver:

Chevigny N. Caractérisation des fonctions de TRCF et de RADA dans l'expression et la maintenance des génomes des organelles chez Arabidopsis thaliana : Characterization of TRCF and RADA functions in the expression and maintenance of organelle genomes in Arabidopsis thaliana. [Internet] [Doctoral dissertation]. Université de Strasbourg; 2019. [cited 2021 Jan 16]. Available from: http://www.theses.fr/2019STRAJ042.

Council of Science Editors:

Chevigny N. Caractérisation des fonctions de TRCF et de RADA dans l'expression et la maintenance des génomes des organelles chez Arabidopsis thaliana : Characterization of TRCF and RADA functions in the expression and maintenance of organelle genomes in Arabidopsis thaliana. [Doctoral Dissertation]. Université de Strasbourg; 2019. Available from: http://www.theses.fr/2019STRAJ042

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