Cdk1 targets Srs2 to complete synthesis-dependent strand annealing and to promote
MARCO, Saporano, Callahan DEVON, Zheng XIUZHONG, Lumír KREJČÍ, Haber JAMES, Klein HANNAH and Liberi GIORDANO. Cdk1 targets Srs2 to complete synthesis-dependent strand annealing and to promote. Online. PLoS Genetics. Public Library of Science, 2010, vol. 2010, No 2, 8 pp. ISSN 1553-7390. [citováno 2024-04-23] |
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Basic information | |
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Original name | Cdk1 targets Srs2 to complete synthesis-dependent strand annealing and to promote |
Name in Czech | Cdk1 targets Srs2 to complete synthesis-dependent strand annealing and to promote |
Authors | MARCO, Saporano (380 Italy), Callahan DEVON (840 United States of America), Zheng XIUZHONG (840 United States of America), Lumír KREJČÍ (203 Czech Republic, guarantor, belonging to the institution), Haber JAMES (840 United States of America), Klein HANNAH (840 United States of America) and Liberi GIORDANO (380 Italy) |
Edition | PLoS Genetics, Public Library of Science, 2010, 1553-7390. |
Other information | |
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Original language | English |
Type of outcome | Article in a journal |
Field of Study | 10600 1.6 Biological sciences |
Country of publisher | United States of America |
Confidentiality degree | is not subject to a state or trade secret |
Impact factor | Impact factor: 9.543 |
RIV identification code | RIV/00216224:14110/10:00043106 |
Organization unit | Faculty of Medicine |
UT WoS | 000275262700009 |
Keywords in English | DNA repair; DNA damage; replication; genomic instability |
Tags | International impact, Reviewed |
Changed by | Changed by: doc. Mgr. Lumír Krejčí, Ph.D., učo 18098. Changed: 19/1/2011 05:38. |
Abstract |
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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. |
Abstract (in Czech) |
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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. |
Links | |
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GA301/09/1917, research and development project | Name: Štěpení replikačních-rekombinačních DNA meziproduktů a jejich úloha při nestabilitě genomu |
Investor: Czech Science Foundation | |
GD203/09/H046, research and development project | Name: Biochemie na rozcestí mezi in silico a in vitro |
Investor: Czech Science Foundation | |
ME10048, research and development project | Name: Vliv post-translačních modifikací na DNA opravu a rekombinaci. |
Investor: Ministry of Education, Youth and Sports of the CR, Research and Development Programme KONTAKT (ME) | |
MSM0021622413, plan (intention) | Name: Proteiny v metabolismu a při interakci organismů s prostředím |
Investor: Ministry of Education, Youth and Sports of the CR, Proteins in metabolism and interaction of organisms with the environment |
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