The Function and Regulation of REV7 in DNA Repair Pathway Choice
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Clairmont, Connor S
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CitationClairmont, Connor S. 2021. The Function and Regulation of REV7 in DNA Repair Pathway Choice. Doctoral dissertation, Harvard University Graduate School of Arts and Sciences.
AbstractDNA damage is a major threat facing our cells on a daily basis. Failure to properly repair
damaged DNA can lead to the development of cancer. REV7 is a small protein that is essential
for two highly distinct DNA repair pathways: double strand break (DSB) repair and translesion
DNA synthesis (TLS). While the TLS function of REV7 has been known for many years, its
involvement in DSB repair and potentially other pathways in just beginning to be unraveled. In
this work I investigate the function and regulation or REV7 in two new contexts, the Fanconi
Anemia (FA) pathway and in DSB repair. I demonstrate the existence of the novel REV7 binding
partner FAM35A/SHLD2 and show that it is an essential player specifically in the DSB repair
branch of REV7 function. I further reveal a unique mechanism of regulation of REV7 dictated by
stable conformational changes, which are controlled in part by the ATPase TRIP13 and its
adaptor subunit p31. By actively remodeling REV7, TRIP13-p31 promote the inactivation of
REV7-dependent complexes, promoting the usage of higher-fidelity alternatives to REV7-
dependent pathways. Overall, this work reveals a new degree of complexity and importance of
the REV7 protein in controlling DNA repair pathway choice in multiple contexts.
Citable link to this pagehttps://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37368251
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