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You searched for +publisher:"University of Toronto" +contributor:("Mekhail, Karim"). Showing records 1 – 3 of 3 total matches.

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University of Toronto

1. Chung, Daniel. Perinuclear Tethers License Telomeric DSBs for a Broad Kinesin- and NPC-dependent DNA Repair Process.

Degree: 2015, University of Toronto

DNA double-strand breaks (DSBs) are often targeted to nuclear pore complexes (NPCs) for repair. We show that the Kinesin-14 motor protein complex (Cik1-Kar3) cooperates with chromatin remodellers to mediate interactions between subtelomeric DSBs and the Nup84 nuclear pore complex to ensure cell survival via break-induced replication (BIR), an error prone DNA repair process. Insertion of a DNA zip code near the subtelomeric DSB site artificially targets it to NPCs hyperactivating this repair mechanism. Repair of non-telomeric DSBs by BIR depend on Kinesin-14 and Nup84, but not perinuclear telomere tethers. However, we show that Kinesin-14 in general and more specifically its catalytic activity is needed for the targeting and release of DSBs to and from Nup84, respectively. Thus, we uncover roles for kinesin and NPCs in DNA repair by BIR and reveal that perinuclear telomere anchors license subtelomeric DSBs for this error-prone DNA repair mechanism.

M.Sc.

2016-11-24 00:00:00

Advisors/Committee Members: Mekhail, Karim, Laboratory Medicine and Pathobiology.

Subjects/Keywords: 0307

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

APA (6th Edition):

Chung, D. (2015). Perinuclear Tethers License Telomeric DSBs for a Broad Kinesin- and NPC-dependent DNA Repair Process. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/74686

Chicago Manual of Style (16th Edition):

Chung, Daniel. “Perinuclear Tethers License Telomeric DSBs for a Broad Kinesin- and NPC-dependent DNA Repair Process.” 2015. Masters Thesis, University of Toronto. Accessed August 22, 2019. http://hdl.handle.net/1807/74686.

MLA Handbook (7th Edition):

Chung, Daniel. “Perinuclear Tethers License Telomeric DSBs for a Broad Kinesin- and NPC-dependent DNA Repair Process.” 2015. Web. 22 Aug 2019.

Vancouver:

Chung D. Perinuclear Tethers License Telomeric DSBs for a Broad Kinesin- and NPC-dependent DNA Repair Process. [Internet] [Masters thesis]. University of Toronto; 2015. [cited 2019 Aug 22]. Available from: http://hdl.handle.net/1807/74686.

Council of Science Editors:

Chung D. Perinuclear Tethers License Telomeric DSBs for a Broad Kinesin- and NPC-dependent DNA Repair Process. [Masters Thesis]. University of Toronto; 2015. Available from: http://hdl.handle.net/1807/74686


University of Toronto

2. Poon, Betty Po Kei. Roles for the Cohibin Complex and its Associated Factors in the Maintenance of Several Silent Chromatin Domains in S. cerevisiae.

Degree: 2012, University of Toronto

In Saccharomyces cerevisiae, the telomeres and rDNA repeats are repetitive silent chromatin domains that are tightly regulated to maintain silencing and genome stability. Disruption of the Cohibin complex, which maintains rDNA silencing and stability, also abrogates telomere localization and silencing. Cohibin-deficient cells have decreased Sir2 localization at telomeres, and restoring telomeric Sir2 concentrations rescues the telomeric defects observed in Cohibin-deficient cells. Genetic and molecular interactions suggest that Cohibin clusters telomeres to the nuclear envelope by binding inner nuclear membrane proteins. Futhermore, telomeric and rDNA sequences can form G-quadruplex structures. G-quadruplexes are non-canonical DNA structures that have been linked to processes affecting chromosome stability. Disruption of the G-quadruplex stabilizing protein Stm1, which also interacts with Cohibin, increases rDNA stability without affecting silent chromatin formation. In all, our findings have led to the discovery of new processes involved in the maintenance of repetitive silent chromatin domains that may be conserved across eukaryotes.

MAST

Advisors/Committee Members: Mekhail, Karim, Laboratory Medicine and Pathobiology.

Subjects/Keywords: Cohibin; G-quadruplex; telomere; ribosomal DNA; silent chromatin; genome stability; 0369; 0307

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

APA (6th Edition):

Poon, B. P. K. (2012). Roles for the Cohibin Complex and its Associated Factors in the Maintenance of Several Silent Chromatin Domains in S. cerevisiae. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/33494

Chicago Manual of Style (16th Edition):

Poon, Betty Po Kei. “Roles for the Cohibin Complex and its Associated Factors in the Maintenance of Several Silent Chromatin Domains in S. cerevisiae.” 2012. Masters Thesis, University of Toronto. Accessed August 22, 2019. http://hdl.handle.net/1807/33494.

MLA Handbook (7th Edition):

Poon, Betty Po Kei. “Roles for the Cohibin Complex and its Associated Factors in the Maintenance of Several Silent Chromatin Domains in S. cerevisiae.” 2012. Web. 22 Aug 2019.

Vancouver:

Poon BPK. Roles for the Cohibin Complex and its Associated Factors in the Maintenance of Several Silent Chromatin Domains in S. cerevisiae. [Internet] [Masters thesis]. University of Toronto; 2012. [cited 2019 Aug 22]. Available from: http://hdl.handle.net/1807/33494.

Council of Science Editors:

Poon BPK. Roles for the Cohibin Complex and its Associated Factors in the Maintenance of Several Silent Chromatin Domains in S. cerevisiae. [Masters Thesis]. University of Toronto; 2012. Available from: http://hdl.handle.net/1807/33494


University of Toronto

3. Szafranski, Kirk Matthew James. Yeast Genetic Modeling of Pbp1/ATXN2-linked Neurodegenerative Diseases.

Degree: 2016, University of Toronto

The polyglutamine expansion of the human gene ATXN2 is associated with neurodegenerative diseases including Amyotrophic Lateral Sclerosis (ALS) and Spinocerebellar Ataxia type 2 (SCA2). Work in our lab demonstrated that deletion of the Saccharomyces cerevisiae ATXN2 orthologue Pbp1 results in the accumulation of RNA-DNA hybrids. Here I demonstrate that hybrid accumulation in pbp1Î cells triggers aberrant recombination within the ribosomal DNA (rDNA) repeats and shortening of replicative lifespan. These deleterious phenotypes can be rescued by caloric restriction. To better model disease I created a yeast genetic model of human ATXN2-linked diseases by generating cells expressing polyglutamine-expanded Pbp1. These cells also had shorter replicative lifespan. However, hybrid accumulation or aberrant recombination within the rDNA repeats was unaffected. Instead, these strains demonstrate gross chromosomal rearrangement more substantial than those observed in pbp1Î cells suggesting that replicative lifespan is impacted by distinctive mechanisms in strains lacking Pbp1 or expressing polyglutamine-expanded Pbp1.

M.Sc.

2018-08-08 00:00:00

Advisors/Committee Members: Mekhail, Karim, Laboratory Medicine and Pathobiology.

Subjects/Keywords: ALS; ATXN2; rDNA Repeats; Replicative Lifespan; SCA2; 0307

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

APA (6th Edition):

Szafranski, K. M. J. (2016). Yeast Genetic Modeling of Pbp1/ATXN2-linked Neurodegenerative Diseases. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/90130

Chicago Manual of Style (16th Edition):

Szafranski, Kirk Matthew James. “Yeast Genetic Modeling of Pbp1/ATXN2-linked Neurodegenerative Diseases.” 2016. Masters Thesis, University of Toronto. Accessed August 22, 2019. http://hdl.handle.net/1807/90130.

MLA Handbook (7th Edition):

Szafranski, Kirk Matthew James. “Yeast Genetic Modeling of Pbp1/ATXN2-linked Neurodegenerative Diseases.” 2016. Web. 22 Aug 2019.

Vancouver:

Szafranski KMJ. Yeast Genetic Modeling of Pbp1/ATXN2-linked Neurodegenerative Diseases. [Internet] [Masters thesis]. University of Toronto; 2016. [cited 2019 Aug 22]. Available from: http://hdl.handle.net/1807/90130.

Council of Science Editors:

Szafranski KMJ. Yeast Genetic Modeling of Pbp1/ATXN2-linked Neurodegenerative Diseases. [Masters Thesis]. University of Toronto; 2016. Available from: http://hdl.handle.net/1807/90130

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