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And-1 is required for homologous recombination repair by regulating DNA end resection
Homologous recombination (HR) is a major mechanism to repair DNA double-strand breaks (DSBs). Although tumor suppressor CtIP is critical for DSB end resection, a key initial event of HR repair, the mechanism regulating the recruitment of CtIP to DSB sites remains largely unknown. Here, we show that...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389477/ https://www.ncbi.nlm.nih.gov/pubmed/27940557 http://dx.doi.org/10.1093/nar/gkw1241 |
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author | Li, Yongming Li, Zongzhu Wu, Ruiqin Han, Zhiyong Zhu, Wenge |
author_facet | Li, Yongming Li, Zongzhu Wu, Ruiqin Han, Zhiyong Zhu, Wenge |
author_sort | Li, Yongming |
collection | PubMed |
description | Homologous recombination (HR) is a major mechanism to repair DNA double-strand breaks (DSBs). Although tumor suppressor CtIP is critical for DSB end resection, a key initial event of HR repair, the mechanism regulating the recruitment of CtIP to DSB sites remains largely unknown. Here, we show that acidic nucleoplasmic DNA‐binding protein 1 (And‐1) forms complexes with CtIP as well as other repair proteins, and is essential for HR repair by regulating DSB end resection. Furthermore, And-1 is recruited to DNA DSB sites in a manner dependent on MDC1, BRCA1 and ATM, down-regulation of And-1 impairs end resection by reducing the recruitment of CtIP to damage sites, and considerably reduces Chk1 activation and other damage response during HR repair. These findings collectively demonstrate a hitherto unknown role of MDC1→And-1→CtIP axis that regulates CtIP-mediated DNA end resection and cellular response to DSBs. |
format | Online Article Text |
id | pubmed-5389477 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-53894772017-04-24 And-1 is required for homologous recombination repair by regulating DNA end resection Li, Yongming Li, Zongzhu Wu, Ruiqin Han, Zhiyong Zhu, Wenge Nucleic Acids Res Genome Integrity, Repair and Replication Homologous recombination (HR) is a major mechanism to repair DNA double-strand breaks (DSBs). Although tumor suppressor CtIP is critical for DSB end resection, a key initial event of HR repair, the mechanism regulating the recruitment of CtIP to DSB sites remains largely unknown. Here, we show that acidic nucleoplasmic DNA‐binding protein 1 (And‐1) forms complexes with CtIP as well as other repair proteins, and is essential for HR repair by regulating DSB end resection. Furthermore, And-1 is recruited to DNA DSB sites in a manner dependent on MDC1, BRCA1 and ATM, down-regulation of And-1 impairs end resection by reducing the recruitment of CtIP to damage sites, and considerably reduces Chk1 activation and other damage response during HR repair. These findings collectively demonstrate a hitherto unknown role of MDC1→And-1→CtIP axis that regulates CtIP-mediated DNA end resection and cellular response to DSBs. Oxford University Press 2017-03-17 2016-12-09 /pmc/articles/PMC5389477/ /pubmed/27940557 http://dx.doi.org/10.1093/nar/gkw1241 Text en © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Genome Integrity, Repair and Replication Li, Yongming Li, Zongzhu Wu, Ruiqin Han, Zhiyong Zhu, Wenge And-1 is required for homologous recombination repair by regulating DNA end resection |
title | And-1 is required for homologous recombination repair by regulating DNA end resection |
title_full | And-1 is required for homologous recombination repair by regulating DNA end resection |
title_fullStr | And-1 is required for homologous recombination repair by regulating DNA end resection |
title_full_unstemmed | And-1 is required for homologous recombination repair by regulating DNA end resection |
title_short | And-1 is required for homologous recombination repair by regulating DNA end resection |
title_sort | and-1 is required for homologous recombination repair by regulating dna end resection |
topic | Genome Integrity, Repair and Replication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389477/ https://www.ncbi.nlm.nih.gov/pubmed/27940557 http://dx.doi.org/10.1093/nar/gkw1241 |
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