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

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Publikace nespadá pod Fakultu sportovních studií, ale pod Lékařskou fakultu. Oficiální stránka publikace je na webu muni.cz.
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MARCO Saporano DEVON Callahan XIUZHONG Zheng KREJČÍ Lumír JAMES Haber HANNAH Klein GIORDANO Liberi

Rok publikování 2010
Druh Článek v odborném periodiku
Časopis / Zdroj PLoS Genetics
Fakulta / Pracoviště MU

Lékařská fakulta

Citace
Obor Biochemie
Klíčová slova DNA repair; DNA damage; replication; genomic instability
Popis Cdk1 kinase phosphorylates budding yeast Srs2, a member of UvrD protein family that displays both DNA translocation and DNA unwinding activities in vitro. Srs2 prevents homologous recombination by dismantling Rad51 filaments and it is also required for double strand break repair. Here we examine the biological significance of Cdk1-dependent phosphorylation of Srs2 using mutants that constitutively express the phosphorylated or unphosphorylated isoforms. We found that Cdk1 targets Srs2 to repair double strand break (DSB) after strand invasion. Srs2 phosphorylation is required to complete synthesis-dependent strand annealing pathway, likely controlling the disassembly of the D-loop intermediate. Cdk1 phosphorylation, indeed, controls the turnover of Srs2 protein at the invading strand, while it is not required for that of Rad51. Further analysis on the recombination phenotypes of the srs2 phospho-mutants indicated that Srs2 phosphorylation is not indeed essential for the removal of toxic Rad51 nucleofilaments, while it is plays a role when DNA breaks are channeled into the homologous recombinational repair. Cdk1-targeted Srs2 might have attenuated ability to inhibit recombination and it does not need to interact with PCNA to promote recombinational repair. Finally, we demonstrated that the recombination defects of unphosphorylatable Srs2 are mainly due to the unscheduled accumulation of the protein in a sumoylated form. Thus, Srs2 function in removing toxic Rad51 filaments is separable from its role in promoting recombinational repair, which exclusively depends on Cdk1-dependent phosphorylation. We suggest that Cdk1 kinase counteracts sumoylation and targets Srs2 to dismantle specific DNA structures in a helicase-dependent manner during homologous recombinational repair.
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