Detailed Information on Publication Record
2009
Functional significance of the Rad51-Srs2 complex in Rad51 presynaptic filament disruption.
SIERRA, Colavito, Macris-Kiss MARGARET, Seong CHANGHYUN, Gleeson OLIVE, Greene ERIC C. et. al.Basic information
Original name
Functional significance of the Rad51-Srs2 complex in Rad51 presynaptic filament disruption.
Name in Czech
Functional significance of the Rad51-Srs2 complex in Rad51 presynaptic filament disruption.
Authors
SIERRA, Colavito (840 United States of America), Macris-Kiss MARGARET (840 United States of America), Seong CHANGHYUN (840 United States of America), Gleeson OLIVE (840 United States of America), Greene ERIC C. (840 United States of America), Klein HANNAH L. (840 United States of America), Krejci LUMIR (203 Czech Republic, guarantor) and Sung PATRICK (840 United States of America)
Edition
Nucleic Acids Research, ENGLAND, OXFORD UNIV PRESS, 2009, 0305-1048
Other information
Language
English
Type of outcome
Článek v odborném periodiku
Field of Study
10600 1.6 Biological sciences
Country of publisher
United States of America
Confidentiality degree
není předmětem státního či obchodního tajemství
References:
Impact factor
Impact factor: 7.479
RIV identification code
RIV/00216224:14310/09:00029683
Organization unit
Faculty of Science
UT WoS
000271819900011
Keywords in English
DNA repair; DNA damage; replication; genomic instability
Tags
International impact, Reviewed
Změněno: 15/12/2009 14:59, doc. Mgr. Lumír Krejčí, Ph.D.
V originále
The SRS2 (Suppressor of RAD Six screen mutant 2) gene encodes an ATP-dependent DNA helicase that regulates homologous recombination in Saccharomyces cerevisiae. Mutations in SRS2 result in a hyper-recombination phenotype, sensitivity to DNA damaging agents and synthetic lethality with mutations that affect DNA metabolism. Several of these phenotypes can be suppressed by inactivating genes of the RAD52 epistasis group that promote homologous recombination, implicating inappropriate recombination as the underlying cause of the mutant phenotype. Consistent with the genetic data, purified Srs2 strongly inhibits Rad51-mediated recombination reactions by disrupting the Rad51-ssDNA presynaptic filament. Srs2 interacts with Rad51 in the yeast two-hybrid assay and also in vitro. To investigate the functional relevance of the Srs2-Rad51 complex, we have generated srs2 truncation mutants that retain full ATPase and helicase activities, but differ in their ability to interact with Rad51. Importantly, the srs2 mutant proteins attenuated for Rad51 interaction are much less capable of Rad51 presynaptic filament disruption. An internal deletion in Srs2 likewise diminishes Rad51 interaction and anti-recombinase activity. We also present evidence that deleting the Srs2 C-terminus engenders a hyper-recombination phenotype. These results highlight the importance of Rad51 interaction in the anti-recombinase function of Srs2, and provide evidence that this Srs2 function can be uncoupled from its helicase activity.
In Czech
The SRS2 (Suppressor of RAD Six screen mutant 2) gene encodes an ATP-dependent DNA helicase that regulates homologous recombination in Saccharomyces cerevisiae. Mutations in SRS2 result in a hyper-recombination phenotype, sensitivity to DNA damaging agents and synthetic lethality with mutations that affect DNA metabolism. Several of these phenotypes can be suppressed by inactivating genes of the RAD52 epistasis group that promote homologous recombination, implicating inappropriate recombination as the underlying cause of the mutant phenotype. Consistent with the genetic data, purified Srs2 strongly inhibits Rad51-mediated recombination reactions by disrupting the Rad51-ssDNA presynaptic filament. Srs2 interacts with Rad51 in the yeast two-hybrid assay and also in vitro. To investigate the functional relevance of the Srs2-Rad51 complex, we have generated srs2 truncation mutants that retain full ATPase and helicase activities, but differ in their ability to interact with Rad51. Importantly, the srs2 mutant proteins attenuated for Rad51 interaction are much less capable of Rad51 presynaptic filament disruption. An internal deletion in Srs2 likewise diminishes Rad51 interaction and anti-recombinase activity. We also present evidence that deleting the Srs2 C-terminus engenders a hyper-recombination phenotype. These results highlight the importance of Rad51 interaction in the anti-recombinase function of Srs2, and provide evidence that this Srs2 function can be uncoupled from its helicase activity.
Links
| GA301/09/1917, research and development project |
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| GD203/09/H046, research and development project |
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| LC06030, research and development project |
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| MSM0021622413, plan (intention) |
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