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The effect of telomeric repeats on double-strand break processing and repair

Marcomini, Isabella. The effect of telomeric repeats on double-strand break processing and repair. 2018, Doctoral Thesis, University of Basel, Faculty of Science.

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Official URL: http://edoc.unibas.ch/diss/DissB_12853

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Abstract

Multiple pathways regulate the repair of double-strand breaks (DSBs) to suppress potentially dangerous ectopic recombination. Both sequence and chromatin context are thought to influence pathway choice between non-homologous end-joining (NHEJ) and homology-driven recombination. To test the effect of repetitive sequences on break processing, we have inserted TG-rich repeats on one side of an inducible DSB at the budding yeast MAT locus on chromosome III. Five clustered Rap1 sites within a break-proximal TG repeat are sufficient to block Mre11-Rad50-Xrs2 recruitment, impair resection, and favor elongation by telomerase. The two sides of the break lose end-to-end tethering and show enhanced, uncoordinated movement. Only the TG-free side is resected and shifts to the nuclear periphery. In contrast to persistent DSBs without TG repeats that are repaired by imprecise NHEJ, nearly all survivors of repeat-proximal DSBs repair the break by a homology-driven, non-reciprocal translocation from ChrIII-R to ChrVII-L. This suppression of imprecise NHEJ at TG-repeat-flanked DSBs requires the Uls1 translocase activity.
Advisors:Gasser, Susan M. and Lingner, Joachim
Faculties and Departments:09 Associated Institutions > Friedrich Miescher Institut FMI > Quantitative Biology > Nuclear organization in development and genome stability (Gasser)
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:12853
Thesis status:Complete
Bibsysno:Link to catalogue
Number of Pages:1 Online-Ressource (159 Seiten)
Language:English
Identification Number:
Last Modified:12 Dec 2018 15:21
Deposited On:12 Dec 2018 15:20

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