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FBH1 promotes DNA double-strand breakage and apoptosis in response to DNA replication stress
Proper resolution of stalled replication forks is essential for genome stability. Purification of FBH1, a UvrD DNA helicase, identified a physical interaction with replication protein A (RPA), the major cellular single-stranded DNA (ssDNA)–binding protein complex. Compared with control cells, FBH1-d...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3549964/ https://www.ncbi.nlm.nih.gov/pubmed/23319600 http://dx.doi.org/10.1083/jcb.201209002 |
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author | Jeong, Yeon-Tae Rossi, Mario Cermak, Lukas Saraf, Anita Florens, Laurence Washburn, Michael P. Sung, Patrick Schildkraut, Carl Pagano, Michele |
author_facet | Jeong, Yeon-Tae Rossi, Mario Cermak, Lukas Saraf, Anita Florens, Laurence Washburn, Michael P. Sung, Patrick Schildkraut, Carl Pagano, Michele |
author_sort | Jeong, Yeon-Tae |
collection | PubMed |
description | Proper resolution of stalled replication forks is essential for genome stability. Purification of FBH1, a UvrD DNA helicase, identified a physical interaction with replication protein A (RPA), the major cellular single-stranded DNA (ssDNA)–binding protein complex. Compared with control cells, FBH1-depleted cells responded to replication stress with considerably fewer double-strand breaks (DSBs), a dramatic reduction in the activation of ATM and DNA-PK and phosphorylation of RPA2 and p53, and a significantly increased rate of survival. A minor decrease in ssDNA levels was also observed. All these phenotypes were rescued by wild-type FBH1, but not a FBH1 mutant lacking helicase activity. FBH1 depletion had no effect on other forms of genotoxic stress in which DSBs form by means that do not require ssDNA intermediates. In response to catastrophic genotoxic stress, apoptosis prevents the persistence and propagation of DNA lesions. Our findings show that FBH1 helicase activity is required for the efficient induction of DSBs and apoptosis specifically in response to DNA replication stress. |
format | Online Article Text |
id | pubmed-3549964 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-35499642013-07-21 FBH1 promotes DNA double-strand breakage and apoptosis in response to DNA replication stress Jeong, Yeon-Tae Rossi, Mario Cermak, Lukas Saraf, Anita Florens, Laurence Washburn, Michael P. Sung, Patrick Schildkraut, Carl Pagano, Michele J Cell Biol Research Articles Proper resolution of stalled replication forks is essential for genome stability. Purification of FBH1, a UvrD DNA helicase, identified a physical interaction with replication protein A (RPA), the major cellular single-stranded DNA (ssDNA)–binding protein complex. Compared with control cells, FBH1-depleted cells responded to replication stress with considerably fewer double-strand breaks (DSBs), a dramatic reduction in the activation of ATM and DNA-PK and phosphorylation of RPA2 and p53, and a significantly increased rate of survival. A minor decrease in ssDNA levels was also observed. All these phenotypes were rescued by wild-type FBH1, but not a FBH1 mutant lacking helicase activity. FBH1 depletion had no effect on other forms of genotoxic stress in which DSBs form by means that do not require ssDNA intermediates. In response to catastrophic genotoxic stress, apoptosis prevents the persistence and propagation of DNA lesions. Our findings show that FBH1 helicase activity is required for the efficient induction of DSBs and apoptosis specifically in response to DNA replication stress. The Rockefeller University Press 2013-01-21 /pmc/articles/PMC3549964/ /pubmed/23319600 http://dx.doi.org/10.1083/jcb.201209002 Text en © 2013 Jeong 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 Jeong, Yeon-Tae Rossi, Mario Cermak, Lukas Saraf, Anita Florens, Laurence Washburn, Michael P. Sung, Patrick Schildkraut, Carl Pagano, Michele FBH1 promotes DNA double-strand breakage and apoptosis in response to DNA replication stress |
title | FBH1 promotes DNA double-strand breakage and apoptosis in response to DNA replication stress |
title_full | FBH1 promotes DNA double-strand breakage and apoptosis in response to DNA replication stress |
title_fullStr | FBH1 promotes DNA double-strand breakage and apoptosis in response to DNA replication stress |
title_full_unstemmed | FBH1 promotes DNA double-strand breakage and apoptosis in response to DNA replication stress |
title_short | FBH1 promotes DNA double-strand breakage and apoptosis in response to DNA replication stress |
title_sort | fbh1 promotes dna double-strand breakage and apoptosis in response to dna replication stress |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3549964/ https://www.ncbi.nlm.nih.gov/pubmed/23319600 http://dx.doi.org/10.1083/jcb.201209002 |
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