Cdk1 targets Srs2 to complete synthesis-dependent strand annealing and to promote recombinational repair.

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Show simple item record Saponaro, Marco Callahan, Devon Zheng, Xiuzhong Krejci, Lumir Haber, James E Klein, Hannah L Liberi, Giordano 2019-01-29T18:18:28Z 2019-01-29T18:18:28Z 2010
dc.identifier.issn 1553-7390
dc.identifier.issn 1553-7404
dc.description.abstract Cdk1 kinase phosphorylates budding yeast Srs2, a member of UvrD protein family, displays both DNA translocation and DNA unwinding activities in vitro. Srs2 prevents homologous recombination by dismantling Rad51 filaments and is also required for double-strand break (DSB) repair. Here we examine the biological significance of Cdk1-dependent phosphorylation of Srs2, using mutants that constitutively express the phosphorylated or unphosphorylated protein isoforms. We found that Cdk1 targets Srs2 to repair DSB and, in particular, to complete synthesis-dependent strand annealing, likely controlling the disassembly of a D-loop intermediate. Cdk1-dependent phosphorylation controls turnover of Srs2 at the invading strand; and, in absence of this modification, the turnover of Rad51 is not affected. Further analysis of the recombination phenotypes of the srs2 phospho-mutants showed that Srs2 phosphorylation is not required for the removal of toxic Rad51 nucleofilaments, although it is essential for cell survival, when DNA breaks are channeled into homologous recombinational repair. Cdk1-targeted Srs2 displays a PCNA-independent role and appears to have an attenuated ability to inhibit recombination. Finally, the recombination defects of unphosphorylatable Srs2 are primarily due to unscheduled accumulation of the Srs2 protein in a sumoylated form. Thus, the Srs2 anti-recombination function in removing toxic Rad51 filaments is genetically separable from its role in promoting recombinational repair, which depends exclusively on Cdk1-dependent phosphorylation. We suggest that Cdk1 kinase counteracts unscheduled sumoylation of Srs2 and targets Srs2 to dismantle specific DNA structures, such as the D-loops, in a helicase-dependent manner during homologous recombinational repair.
dc.format.extent 1 file
dc.language English
dc.language.iso eng
dc.publisher Public Library of Science
dc.rights Creative Commons Attribution 4.0 International License
dc.subject CDC28 Protein Kinase, S cerevisiae
dc.subject Consensus Sequence
dc.subject DNA Breaks, Double-Stranded
dc.subject DNA Helicases
dc.subject DNA Repair
dc.subject DNA, Fungal
dc.subject Microbial Viability
dc.subject Models, Biological
dc.subject Mutation
dc.subject Phosphorylation
dc.subject Proliferating Cell Nuclear Antigen
dc.subject Protein Binding
dc.subject Protein Processing, Post-Translational
dc.subject Rad51 Recombinase
dc.subject Recombination, Genetic
dc.title Cdk1 targets Srs2 to complete synthesis-dependent strand annealing and to promote recombinational repair.
dc.type Article
dc.contributor.department Department of Biology
dc.relation.journal PLoS Genetics
dc.identifier.pmid 20195513
dc.identifier.pmcid PMC2829061
dc.description.esploro yes

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