MARCO, Saporano, Callahan DEVON, Zheng XIUZHONG, Lumír KREJČÍ, Haber JAMES, Klein HANNAH a Liberi GIORDANO. Cdk1 targets Srs2 to complete synthesis-dependent strand annealing and to promote. PLoS Genetics, Public Library of Science, 2010, roč. 2010, č. 2. ISSN 1553-7390.
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Základní údaje
Originální název Cdk1 targets Srs2 to complete synthesis-dependent strand annealing and to promote
Název česky Cdk1 targets Srs2 to complete synthesis-dependent strand annealing and to promote
Autoři MARCO, Saporano (380 Itálie), Callahan DEVON (840 Spojené státy americké), Zheng XIUZHONG (840 Spojené státy americké), Lumír KREJČÍ (203 Česká republika, garant, domácí), Haber JAMES (840 Spojené státy americké), Klein HANNAH (840 Spojené státy americké) a Liberi GIORDANO (380 Itálie).
Vydání PLoS Genetics, Public Library of Science, 2010, 1553-7390.
Další údaje
Originální jazyk angličtina
Typ výsledku Článek v odborném periodiku
Obor 1.6 Biological sciences
Stát vydavatele Spojené státy americké
Utajení není předmětem státního či obchodního tajemství
Impakt faktor Impact factor: 9.543
Kód RIV RIV/00216224:14110/10:00043106
Organizační jednotka Lékařská fakulta
UT WoS 000275262700009
Klíčová slova anglicky DNA repair; DNA damage; replication; genomic instability
Příznaky Mezinárodní význam, Recenzováno
Změnil Změnil: doc. Mgr. Lumír Krejčí, Ph.D., učo 18098. Změněno: 19. 1. 2011 05:38.
Anotace
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.
Anotace česky
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.
Návaznosti
GA301/09/1917, projekt VaVNázev: Štěpení replikačních-rekombinačních DNA meziproduktů a jejich úloha při nestabilitě genomu
Investor: Grantová agentura ČR, Standardní projekty
GD203/09/H046, projekt VaVNázev: Biochemie na rozcestí mezi in silico a in vitro
Investor: Grantová agentura ČR, Doktorské granty
ME10048, projekt VaVNázev: Vliv post-translačních modifikací na DNA opravu a rekombinaci.
Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Program KONTAKT (ME + MEB) (jen po projekty s počátkem řešení v roce 2010), Program výzkumu a vývoje KONTAKT (ME)
MSM0021622413, záměrNázev: Proteiny v metabolismu a při interakci organismů s prostředím
Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Výzkumné záměry
VytisknoutZobrazeno: 23. 10. 2019 02:14