Phosphorylation of Exo1 modulates homologous recombination repair of DNA double-strand breaks

Bolderson, Emma, Tomimatsu, Nozomi, Richard, Derek J., Boucher, Didier, Kumar, Rakesh, Pandita, Tej K., Burma, Sandeep and Khanna, Kum Kum (2010) Phosphorylation of Exo1 modulates homologous recombination repair of DNA double-strand breaks. Nucleic Acids Research, 38 6: 1821-1831. doi:10.1093/nar/gkp1164

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Author Bolderson, Emma
Tomimatsu, Nozomi
Richard, Derek J.
Boucher, Didier
Kumar, Rakesh
Pandita, Tej K.
Burma, Sandeep
Khanna, Kum Kum
Title Phosphorylation of Exo1 modulates homologous recombination repair of DNA double-strand breaks
Journal name Nucleic Acids Research   Check publisher's open access policy
ISSN 0305-1048
Publication date 2010-04
Year available 2009
Sub-type Article (original research)
DOI 10.1093/nar/gkp1164
Open Access Status DOI
Volume 38
Issue 6
Start page 1821
End page 1831
Total pages 11
Editor Keith Fox
Barry Stoddard
Place of publication Oxford, U.K.
Publisher Oxford University Press
Collection year 2011
Language eng
Formatted abstract
DNA double-strand break (DSB) repair via the homologous recombination pathway is a multi-stage process, which results in repair of the DSB without loss of genetic information or fidelity. One essential step in this process is the generation of extended single-stranded DNA (ssDNA) regions at the break site. This ssDNA serves to induce cell cycle checkpoints and is required for Rad51 mediated strand invasion of the sister chromatid. Here, we show that human Exonuclease 1 (Exo1) is required for the normal repair of DSBs by HR. Cells depleted of Exo1 show chromosomal instability and hypersensitivity to ionising radiation (IR) exposure. We find that Exo1 accumulates rapidly at DSBs and is required for the recruitment of RPA and Rad51 to sites of DSBs, suggesting a role for Exo1 in ssDNA generation. Interestingly, the phosphorylation of Exo1 by ATM appears to regulate the activity of Exo1 following resection, allowing optimal Rad51 loading and the completion of HR repair. These data establish a role for Exo1 in resection of DSBs in human cells, highlighting the critical requirement of Exo1 for DSB repair via HR and thus the maintenance of genomic stability.
© The Author(s) 2009. Published by Oxford University Press.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keyword Human Exonuclease 1
Genomic stability
Resect DNA
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online 17 December 2009.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Medicine Publications
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Created: Fri, 01 Apr 2011, 09:04:38 EST by Debbie Banks on behalf of School of Medicine