Cdk1 targets Srs2 to complete synthesis-dependent strand annealing and to promote
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, 8 s. ISSN 1553-7390. |
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Základní údaje | |
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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), Zheng XIUZHONG (840 Spojené státy), Lumír KREJČÍ (203 Česká republika, garant, domácí), Haber JAMES (840 Spojené státy), Klein HANNAH (840 Spojené státy) a Liberi GIORDANO (380 Itálie). |
Vydání | PLoS Genetics, Public Library of Science, 2010, 1553-7390. |
Další údaje | |
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Originální jazyk | angličtina |
Typ výsledku | Článek v odborném periodiku |
Obor | 10600 1.6 Biological sciences |
Stát vydavatele | Spojené státy |
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 |
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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 |
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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 | |
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GA301/09/1917, projekt VaV | Název: Štěpení replikačních-rekombinačních DNA meziproduktů a jejich úloha při nestabilitě genomu |
Investor: Grantová agentura ČR, Štěpení replikačních-rekombinačních DNA meziproduktů a jejich úloha při nestabilitě genomu | |
GD203/09/H046, projekt VaV | Název: Biochemie na rozcestí mezi in silico a in vitro |
Investor: Grantová agentura ČR, Biochemie na rozcestí mezi in silico a in vitro | |
ME10048, projekt VaV | Název: Vliv post-translačních modifikací na DNA opravu a rekombinaci. |
Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Vliv post-translačních modifikací na DNA opravu a rekombinaci., Program výzkumu a vývoje KONTAKT (ME) | |
MSM0021622413, záměr | Název: Proteiny v metabolismu a při interakci organismů s prostředím |
Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Proteiny v metabolismu a při interakci organismů s prostředím |
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