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Phosphorylation of Exo1 modulates homologous recombination repair of DNA double-strand breaks
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 brea...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2847229/ https://www.ncbi.nlm.nih.gov/pubmed/20019063 http://dx.doi.org/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 |
author_facet | Bolderson, Emma Tomimatsu, Nozomi Richard, Derek J. Boucher, Didier Kumar, Rakesh Pandita, Tej K. Burma, Sandeep Khanna, Kum Kum |
author_sort | Bolderson, Emma |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-2847229 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-28472292010-04-01 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 Khanna, Kum Kum Nucleic Acids Res Genome Integrity, Repair and Replication 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. Oxford University Press 2010-04 2009-12-17 /pmc/articles/PMC2847229/ /pubmed/20019063 http://dx.doi.org/10.1093/nar/gkp1164 Text en © The Author(s) 2009. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/2.5 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Genome Integrity, Repair and Replication Bolderson, Emma Tomimatsu, Nozomi Richard, Derek J. Boucher, Didier Kumar, Rakesh Pandita, Tej K. Burma, Sandeep Khanna, Kum Kum Phosphorylation of Exo1 modulates homologous recombination repair of DNA double-strand breaks |
title | Phosphorylation of Exo1 modulates homologous recombination repair of DNA double-strand breaks |
title_full | Phosphorylation of Exo1 modulates homologous recombination repair of DNA double-strand breaks |
title_fullStr | Phosphorylation of Exo1 modulates homologous recombination repair of DNA double-strand breaks |
title_full_unstemmed | Phosphorylation of Exo1 modulates homologous recombination repair of DNA double-strand breaks |
title_short | Phosphorylation of Exo1 modulates homologous recombination repair of DNA double-strand breaks |
title_sort | phosphorylation of exo1 modulates homologous recombination repair of dna double-strand breaks |
topic | Genome Integrity, Repair and Replication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2847229/ https://www.ncbi.nlm.nih.gov/pubmed/20019063 http://dx.doi.org/10.1093/nar/gkp1164 |
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