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RAD51C facilitates checkpoint signaling by promoting CHK2 phosphorylation

The RAD51 paralogues act in the homologous recombination (HR) pathway of DNA repair. Human RAD51C (hRAD51C) participates in branch migration and Holliday junction resolution and thus is important for processing HR intermediates late in the DNA repair process. Evidence for early involvement of RAD51...

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Autores principales: Badie, Sophie, Liao, Chunyan, Thanasoula, Maria, Barber, Paul, Hill, Mark A., Tarsounas, Madalena
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2711581/
https://www.ncbi.nlm.nih.gov/pubmed/19451272
http://dx.doi.org/10.1083/jcb.200811079
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author Badie, Sophie
Liao, Chunyan
Thanasoula, Maria
Barber, Paul
Hill, Mark A.
Tarsounas, Madalena
author_facet Badie, Sophie
Liao, Chunyan
Thanasoula, Maria
Barber, Paul
Hill, Mark A.
Tarsounas, Madalena
author_sort Badie, Sophie
collection PubMed
description The RAD51 paralogues act in the homologous recombination (HR) pathway of DNA repair. Human RAD51C (hRAD51C) participates in branch migration and Holliday junction resolution and thus is important for processing HR intermediates late in the DNA repair process. Evidence for early involvement of RAD51 during DNA repair also exists, but its function in this context is not understood. In this study, we demonstrate that RAD51C accumulates at DNA damage sites concomitantly with the RAD51 recombinase and is retained after RAD51 disassembly, which is consistent with both an early and a late function for RAD51C. RAD51C recruitment depends on ataxia telangiectasia mutated, NBS1, and replication protein A, indicating it functions after DNA end resection but before RAD51 assembly. Furthermore, we find that RAD51C is required for activation of the checkpoint kinase CHK2 and cell cycle arrest in response to DNA damage. This suggests that hRAD51C contributes to the protection of genome integrity by transducing DNA damage signals in addition to engaging the HR machinery.
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spelling pubmed-27115812009-11-18 RAD51C facilitates checkpoint signaling by promoting CHK2 phosphorylation Badie, Sophie Liao, Chunyan Thanasoula, Maria Barber, Paul Hill, Mark A. Tarsounas, Madalena J Cell Biol Research Articles The RAD51 paralogues act in the homologous recombination (HR) pathway of DNA repair. Human RAD51C (hRAD51C) participates in branch migration and Holliday junction resolution and thus is important for processing HR intermediates late in the DNA repair process. Evidence for early involvement of RAD51 during DNA repair also exists, but its function in this context is not understood. In this study, we demonstrate that RAD51C accumulates at DNA damage sites concomitantly with the RAD51 recombinase and is retained after RAD51 disassembly, which is consistent with both an early and a late function for RAD51C. RAD51C recruitment depends on ataxia telangiectasia mutated, NBS1, and replication protein A, indicating it functions after DNA end resection but before RAD51 assembly. Furthermore, we find that RAD51C is required for activation of the checkpoint kinase CHK2 and cell cycle arrest in response to DNA damage. This suggests that hRAD51C contributes to the protection of genome integrity by transducing DNA damage signals in addition to engaging the HR machinery. The Rockefeller University Press 2009-05-18 /pmc/articles/PMC2711581/ /pubmed/19451272 http://dx.doi.org/10.1083/jcb.200811079 Text en © 2009 Badie et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Badie, Sophie
Liao, Chunyan
Thanasoula, Maria
Barber, Paul
Hill, Mark A.
Tarsounas, Madalena
RAD51C facilitates checkpoint signaling by promoting CHK2 phosphorylation
title RAD51C facilitates checkpoint signaling by promoting CHK2 phosphorylation
title_full RAD51C facilitates checkpoint signaling by promoting CHK2 phosphorylation
title_fullStr RAD51C facilitates checkpoint signaling by promoting CHK2 phosphorylation
title_full_unstemmed RAD51C facilitates checkpoint signaling by promoting CHK2 phosphorylation
title_short RAD51C facilitates checkpoint signaling by promoting CHK2 phosphorylation
title_sort rad51c facilitates checkpoint signaling by promoting chk2 phosphorylation
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2711581/
https://www.ncbi.nlm.nih.gov/pubmed/19451272
http://dx.doi.org/10.1083/jcb.200811079
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