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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...

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Autores principales: Kim, Jong-Soo, Krasieva, Tatiana B., Kurumizaka, Hitoshi, Chen, David J., Taylor, A. Malcolm R., Yokomori, Kyoko
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2005
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.
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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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