The yeast Shu complex utilizes homologous recombination machinery for error-free lesion bypass via physical interaction with a Rad51 paralogue

PloS One
Xin XuWei Xiao

Abstract

DNA-damage tolerance (DDT) is defined as a mechanism by which eukaryotic cells resume DNA synthesis to fill the single-stranded DNA gaps left by replication-blocking lesions. Eukaryotic cells employ two different means of DDT, namely translesion DNA synthesis (TLS) and template switching, both of which are coordinately regulated through sequential ubiquitination of PCNA at the K164 residue. In the budding yeast Saccharomyces cerevisiae, the same PCNA-K164 residue can also be sumoylated, which recruits the Srs2 helicase to prevent undesired homologous recombination (HR). While the mediation of TLS by PCNA monoubiquitination has been extensively characterized, the method by which K63-linked PCNA polyubiquitination leads to template switching remains unclear. We recently identified a yeast heterotetrameric Shu complex that couples error-free DDT to HR as a critical step of template switching. Here we report that the Csm2 subunit of Shu physically interacts with Rad55, an accessory protein involved in HR. Rad55 and Rad57 are Rad51 paralogues and form a heterodimer to promote Rad51-ssDNA filament formation by antagonizing Srs2 activity. Although Rad55-Rad57 and Shu function in the same pathway and both act to inhibit Srs2 activity, ...Continue Reading

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Citations

Jul 29, 2015·Nature Communications·William A GainesKara A Bernstein
Jun 5, 2015·Mutation Research. Reviews in Mutation Research·Xin XuWei Xiao
Jun 15, 2016·Nucleic Acids Research·Stephen K GodinKara A Bernstein
Sep 4, 2016·FEMS Yeast Research·Julieta Martino, Kara A Bernstein
Oct 27, 2017·Nucleic Acids Research·Shicheng ZhangJianping Ding
Sep 1, 2015·World Journal of Biological Chemistry·Xin Bi
May 29, 2018·Molecular Systems Biology·J Javier Díaz-MejíaFrederick P Roth
Jul 30, 2020·The Biochemical Journal·Li FanWei Xiao
May 26, 2016·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Stephen K GodinKara A Bernstein
Aug 7, 2019·Nature Communications·Joel C RosenbaumKara A Bernstein
Feb 6, 2020·Nucleic Acids Research·Tomio S TakahashiHelle D Ulrich
Jul 15, 2020·Annual Review of Genetics·Braulio BonillaKara A Bernstein

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Methods Mentioned

BETA
X-ray
two-hybrid
Y2H
Coimmunoprecipitation
immunoprecipitation
ubiquitination
diubiquitination
PCR

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