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The Shu complex is a conserved regulator of Rad51 filament formation

Godin, Stephen K. (2016) The Shu complex is a conserved regulator of Rad51 filament formation. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

The budding yeast Shu complex, a heterotetramer of Shu1, Shu2, Csm2, and Psy3, is important for homologous recombination (HR)-mediated chromosome damage repair and was first characterized a decade ago as promoting Rad51-dependent HR in response to replicative stress, but its mechanistic function and conservation in eukaryotes has remained unknown. Here we provide evidence that the Shu complex is evolutionarily conserved throughout eukaryotes, where it is comprised of a clear Shu2 orthologue physically associating with Rad51 paralogues. The Shu complex itself physically interacts with the rest of the HR machinery during DNA damage repair. Finally, we uncover that the mechanistic function of the Shu complex as a stimulatory co-factor of Rad51 filament formation in vitro, likely explaining the in vivo function of the eukaryotic Shu complex in suppressing error-prone repair. Moving forward, our findings provide a framework for studying the function of the human Shu complex, which will have broad importance in our understanding of DNA damage repair.

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Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Godin, Stephen K.skg33@pitt.eduSKG33
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorBernstein, Kara A.karab@pitt.eduKARAB
Committee ChairOpresko, Patricia Lplo4@pitt.eduPLO4
Committee MemberVanDemark, Andrew P.andyv@pitt.eduANDYV
Committee MemberVan Houten, Bennettvanhoutenb@upmc.eduBEV15
Committee MemberYanowitz, Judithyanowitzjl@mwri.magee.eduJLY23
Date: 29 April 2016
Date Type: Publication
Defense Date: 7 December 2015
Approval Date: 29 April 2016
Submission Date: 10 January 2016
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 169
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Molecular Genetics and Developmental Biology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: DNA damage repair, Homologous recombination, Shu complex, yeast
Date Deposited: 29 Apr 2016 20:02
Last Modified: 19 Dec 2016 14:43
URI: http://d-scholarship.pitt.edu/id/eprint/26709

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