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dc.contributor.advisorD'Andrea, Alan D
dc.contributor.advisorPellman, David
dc.contributor.authorClairmont, Connor S
dc.date.accessioned2021-07-13T04:45:28Z
dc.date.created2021
dc.date.issued2021-05-14
dc.date.submitted2021-05
dc.identifier.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.
dc.identifier.other28495977
dc.identifier.urihttps://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37368251*
dc.description.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.
dc.format.mimetypeapplication/pdf
dc.language.isoen
dash.licenseLAA
dc.subjectBiology
dc.titleThe Function and Regulation of REV7 in DNA Repair Pathway Choice
dc.typeThesis or Dissertation
dash.depositing.authorClairmont, Connor S
dc.date.available2021-07-13T04:45:28Z
thesis.degree.date2021
thesis.degree.grantorHarvard University Graduate School of Arts and Sciences
thesis.degree.levelDoctoral
thesis.degree.namePh.D.
dc.contributor.committeeMemberDurocher, Daniel
dc.contributor.committeeMemberWalker, Graham
dc.contributor.committeeMemberWeinstock, David
dc.type.materialtext
thesis.degree.departmentMedical Sciences
dc.identifier.orcid0000-0003-2302-8906
dash.author.emailclairmont.connor@gmail.com


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