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Drosophila ATM and ATR have distinct activities in the regulation of meiotic DNA damage and repair
Ataxia telangiectasia–mutated (ATM) and ataxia telangiectasia–related (ATR) kinases are conserved regulators of cellular responses to double strand breaks (DSBs). During meiosis, however, the functions of these kinases in DSB repair and the deoxyribonucleic acid (DNA) damage checkpoint are unclear....
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3206348/ https://www.ncbi.nlm.nih.gov/pubmed/22024169 http://dx.doi.org/10.1083/jcb.201104121 |
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author | Joyce, Eric F. Pedersen, Michael Tiong, Stanley White-Brown, Sanese K. Paul, Anshu Campbell, Shelagh D. McKim, Kim S. |
author_facet | Joyce, Eric F. Pedersen, Michael Tiong, Stanley White-Brown, Sanese K. Paul, Anshu Campbell, Shelagh D. McKim, Kim S. |
author_sort | Joyce, Eric F. |
collection | PubMed |
description | Ataxia telangiectasia–mutated (ATM) and ataxia telangiectasia–related (ATR) kinases are conserved regulators of cellular responses to double strand breaks (DSBs). During meiosis, however, the functions of these kinases in DSB repair and the deoxyribonucleic acid (DNA) damage checkpoint are unclear. In this paper, we show that ATM and ATR have unique roles in the repair of meiotic DSBs in Drosophila melanogaster. ATR mutant analysis indicated that it is required for checkpoint activity, whereas ATM may not be. Both kinases phosphorylate H2AV (γ-H2AV), and, using this as a reporter for ATM/ATR activity, we found that the DSB repair response is surprisingly dynamic at the site of DNA damage. γ-H2AV is continuously exchanged, requiring new phosphorylation at the break site until repair is completed. However, most surprising is that the number of γ-H2AV foci is dramatically increased in the absence of ATM, but not ATR, suggesting that the number of DSBs is increased. Thus, we conclude that ATM is primarily required for the meiotic DSB repair response, which includes functions in DNA damage repair and negative feedback control over the level of programmed DSBs during meiosis. |
format | Online Article Text |
id | pubmed-3206348 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-32063482012-04-30 Drosophila ATM and ATR have distinct activities in the regulation of meiotic DNA damage and repair Joyce, Eric F. Pedersen, Michael Tiong, Stanley White-Brown, Sanese K. Paul, Anshu Campbell, Shelagh D. McKim, Kim S. J Cell Biol Research Articles Ataxia telangiectasia–mutated (ATM) and ataxia telangiectasia–related (ATR) kinases are conserved regulators of cellular responses to double strand breaks (DSBs). During meiosis, however, the functions of these kinases in DSB repair and the deoxyribonucleic acid (DNA) damage checkpoint are unclear. In this paper, we show that ATM and ATR have unique roles in the repair of meiotic DSBs in Drosophila melanogaster. ATR mutant analysis indicated that it is required for checkpoint activity, whereas ATM may not be. Both kinases phosphorylate H2AV (γ-H2AV), and, using this as a reporter for ATM/ATR activity, we found that the DSB repair response is surprisingly dynamic at the site of DNA damage. γ-H2AV is continuously exchanged, requiring new phosphorylation at the break site until repair is completed. However, most surprising is that the number of γ-H2AV foci is dramatically increased in the absence of ATM, but not ATR, suggesting that the number of DSBs is increased. Thus, we conclude that ATM is primarily required for the meiotic DSB repair response, which includes functions in DNA damage repair and negative feedback control over the level of programmed DSBs during meiosis. The Rockefeller University Press 2011-10-31 /pmc/articles/PMC3206348/ /pubmed/22024169 http://dx.doi.org/10.1083/jcb.201104121 Text en © 2011 Joyce 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.rupress.org/terms). 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 Joyce, Eric F. Pedersen, Michael Tiong, Stanley White-Brown, Sanese K. Paul, Anshu Campbell, Shelagh D. McKim, Kim S. Drosophila ATM and ATR have distinct activities in the regulation of meiotic DNA damage and repair |
title | Drosophila ATM and ATR have distinct activities in the regulation of meiotic DNA damage and repair |
title_full | Drosophila ATM and ATR have distinct activities in the regulation of meiotic DNA damage and repair |
title_fullStr | Drosophila ATM and ATR have distinct activities in the regulation of meiotic DNA damage and repair |
title_full_unstemmed | Drosophila ATM and ATR have distinct activities in the regulation of meiotic DNA damage and repair |
title_short | Drosophila ATM and ATR have distinct activities in the regulation of meiotic DNA damage and repair |
title_sort | drosophila atm and atr have distinct activities in the regulation of meiotic dna damage and repair |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3206348/ https://www.ncbi.nlm.nih.gov/pubmed/22024169 http://dx.doi.org/10.1083/jcb.201104121 |
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