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DNA damage signaling in response to double-strand breaks during mitosis
The signaling cascade initiated in response to DNA double-strand breaks (DSBs) has been extensively investigated in interphase cells. Here, we show that mitotic cells treated with DSB-inducing agents activate a “primary” DNA damage response (DDR) comprised of early signaling events, including activa...
Autores principales: | , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2930281/ https://www.ncbi.nlm.nih.gov/pubmed/20660628 http://dx.doi.org/10.1083/jcb.200911156 |
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author | Giunta, Simona Belotserkovskaya, Rimma Jackson, Stephen P. |
author_facet | Giunta, Simona Belotserkovskaya, Rimma Jackson, Stephen P. |
author_sort | Giunta, Simona |
collection | PubMed |
description | The signaling cascade initiated in response to DNA double-strand breaks (DSBs) has been extensively investigated in interphase cells. Here, we show that mitotic cells treated with DSB-inducing agents activate a “primary” DNA damage response (DDR) comprised of early signaling events, including activation of the protein kinases ataxia telangiectasia mutated (ATM) and DNA-dependent protein kinase (DNA-PK), histone H2AX phosphorylation together with recruitment of mediator of DNA damage checkpoint 1 (MDC1), and the Mre11–Rad50–Nbs1 (MRN) complex to damage sites. However, mitotic cells display no detectable recruitment of the E3 ubiquitin ligases RNF8 and RNF168, or accumulation of 53BP1 and BRCA1, at DSB sites. Accordingly, we found that DNA-damage signaling is attenuated in mitotic cells, with full DDR activation only ensuing when a DSB-containing mitotic cell enters G1. Finally, we present data suggesting that induction of a primary DDR in mitosis is important because transient inactivation of ATM and DNA-PK renders mitotic cells hypersensitive to DSB-inducing agents. |
format | Text |
id | pubmed-2930281 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-29302812011-01-26 DNA damage signaling in response to double-strand breaks during mitosis Giunta, Simona Belotserkovskaya, Rimma Jackson, Stephen P. J Cell Biol Research Articles The signaling cascade initiated in response to DNA double-strand breaks (DSBs) has been extensively investigated in interphase cells. Here, we show that mitotic cells treated with DSB-inducing agents activate a “primary” DNA damage response (DDR) comprised of early signaling events, including activation of the protein kinases ataxia telangiectasia mutated (ATM) and DNA-dependent protein kinase (DNA-PK), histone H2AX phosphorylation together with recruitment of mediator of DNA damage checkpoint 1 (MDC1), and the Mre11–Rad50–Nbs1 (MRN) complex to damage sites. However, mitotic cells display no detectable recruitment of the E3 ubiquitin ligases RNF8 and RNF168, or accumulation of 53BP1 and BRCA1, at DSB sites. Accordingly, we found that DNA-damage signaling is attenuated in mitotic cells, with full DDR activation only ensuing when a DSB-containing mitotic cell enters G1. Finally, we present data suggesting that induction of a primary DDR in mitosis is important because transient inactivation of ATM and DNA-PK renders mitotic cells hypersensitive to DSB-inducing agents. The Rockefeller University Press 2010-07-26 /pmc/articles/PMC2930281/ /pubmed/20660628 http://dx.doi.org/10.1083/jcb.200911156 Text en © 2009 Giunta 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 Giunta, Simona Belotserkovskaya, Rimma Jackson, Stephen P. DNA damage signaling in response to double-strand breaks during mitosis |
title | DNA damage signaling in response to double-strand breaks during mitosis |
title_full | DNA damage signaling in response to double-strand breaks during mitosis |
title_fullStr | DNA damage signaling in response to double-strand breaks during mitosis |
title_full_unstemmed | DNA damage signaling in response to double-strand breaks during mitosis |
title_short | DNA damage signaling in response to double-strand breaks during mitosis |
title_sort | dna damage signaling in response to double-strand breaks during mitosis |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2930281/ https://www.ncbi.nlm.nih.gov/pubmed/20660628 http://dx.doi.org/10.1083/jcb.200911156 |
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