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Independent and sequential recruitment of NHEJ and HR factors to DNA damage sites in mammalian cells
Damage recognition by repair/checkpoint factors is the critical first step of the DNA damage response. DNA double strand breaks (DSBs) activate checkpoint signaling and are repaired by nonhomologous end-joining (NHEJ) and homologous recombination (HR) pathways. However, in vivo kinetics of the indiv...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2005
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2171485/ https://www.ncbi.nlm.nih.gov/pubmed/16061690 http://dx.doi.org/10.1083/jcb.200411083 |
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author | Kim, Jong-Soo Krasieva, Tatiana B. Kurumizaka, Hitoshi Chen, David J. Taylor, A. Malcolm R. Yokomori, Kyoko |
author_facet | Kim, Jong-Soo Krasieva, Tatiana B. Kurumizaka, Hitoshi Chen, David J. Taylor, A. Malcolm R. Yokomori, Kyoko |
author_sort | Kim, Jong-Soo |
collection | PubMed |
description | Damage recognition by repair/checkpoint factors is the critical first step of the DNA damage response. DNA double strand breaks (DSBs) activate checkpoint signaling and are repaired by nonhomologous end-joining (NHEJ) and homologous recombination (HR) pathways. However, in vivo kinetics of the individual factor responses and the mechanism of pathway choice are not well understood. We report cell cycle and time course analyses of checkpoint activation by ataxia-telangiectasia mutated and damage site recruitment of the repair factors in response to laser-induced DSBs. We found that MRN acts as a DNA damage marker, continuously localizing at unrepaired damage sites. Damage recognition by NHEJ factors precedes that of HR factors. HR factor recruitment is not influenced by NHEJ factor assembly and occurs throughout interphase. Damage site retention of NHEJ factors is transient, whereas HR factors persist at unrepaired lesions, revealing unique roles of the two pathways in mammalian cells. |
format | Text |
id | pubmed-2171485 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2005 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21714852008-03-05 Independent and sequential recruitment of NHEJ and HR factors to DNA damage sites in mammalian cells Kim, Jong-Soo Krasieva, Tatiana B. Kurumizaka, Hitoshi Chen, David J. Taylor, A. Malcolm R. Yokomori, Kyoko J Cell Biol Research Articles Damage recognition by repair/checkpoint factors is the critical first step of the DNA damage response. DNA double strand breaks (DSBs) activate checkpoint signaling and are repaired by nonhomologous end-joining (NHEJ) and homologous recombination (HR) pathways. However, in vivo kinetics of the individual factor responses and the mechanism of pathway choice are not well understood. We report cell cycle and time course analyses of checkpoint activation by ataxia-telangiectasia mutated and damage site recruitment of the repair factors in response to laser-induced DSBs. We found that MRN acts as a DNA damage marker, continuously localizing at unrepaired damage sites. Damage recognition by NHEJ factors precedes that of HR factors. HR factor recruitment is not influenced by NHEJ factor assembly and occurs throughout interphase. Damage site retention of NHEJ factors is transient, whereas HR factors persist at unrepaired lesions, revealing unique roles of the two pathways in mammalian cells. The Rockefeller University Press 2005-08-01 /pmc/articles/PMC2171485/ /pubmed/16061690 http://dx.doi.org/10.1083/jcb.200411083 Text en Copyright © 2005, The Rockefeller University Press 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 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Kim, Jong-Soo Krasieva, Tatiana B. Kurumizaka, Hitoshi Chen, David J. Taylor, A. Malcolm R. Yokomori, Kyoko Independent and sequential recruitment of NHEJ and HR factors to DNA damage sites in mammalian cells |
title | Independent and sequential recruitment of NHEJ and HR factors to DNA damage sites in mammalian cells |
title_full | Independent and sequential recruitment of NHEJ and HR factors to DNA damage sites in mammalian cells |
title_fullStr | Independent and sequential recruitment of NHEJ and HR factors to DNA damage sites in mammalian cells |
title_full_unstemmed | Independent and sequential recruitment of NHEJ and HR factors to DNA damage sites in mammalian cells |
title_short | Independent and sequential recruitment of NHEJ and HR factors to DNA damage sites in mammalian cells |
title_sort | independent and sequential recruitment of nhej and hr factors to dna damage sites in mammalian cells |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2171485/ https://www.ncbi.nlm.nih.gov/pubmed/16061690 http://dx.doi.org/10.1083/jcb.200411083 |
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