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Spatial organization of the mammalian genome surveillance machinery in response to DNA strand breaks

We show that DNA double-strand breaks (DSBs) induce complex subcompartmentalization of genome surveillance regulators. Chromatin marked by γ-H2AX is occupied by ataxia telangiectasia–mutated (ATM) kinase, Mdc1, and 53BP1. In contrast, repair factors (Rad51, Rad52, BRCA2, and FANCD2), ATM and Rad-3–r...

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Autores principales: Bekker-Jensen, Simon, Lukas, Claudia, Kitagawa, Risa, Melander, Fredrik, Kastan, Michael B., Bartek, Jiri, Lukas, Jiri
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2063811/
https://www.ncbi.nlm.nih.gov/pubmed/16618811
http://dx.doi.org/10.1083/jcb.200510130
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author Bekker-Jensen, Simon
Lukas, Claudia
Kitagawa, Risa
Melander, Fredrik
Kastan, Michael B.
Bartek, Jiri
Lukas, Jiri
author_facet Bekker-Jensen, Simon
Lukas, Claudia
Kitagawa, Risa
Melander, Fredrik
Kastan, Michael B.
Bartek, Jiri
Lukas, Jiri
author_sort Bekker-Jensen, Simon
collection PubMed
description We show that DNA double-strand breaks (DSBs) induce complex subcompartmentalization of genome surveillance regulators. Chromatin marked by γ-H2AX is occupied by ataxia telangiectasia–mutated (ATM) kinase, Mdc1, and 53BP1. In contrast, repair factors (Rad51, Rad52, BRCA2, and FANCD2), ATM and Rad-3–related (ATR) cascade (ATR, ATR interacting protein, and replication protein A), and the DNA clamp (Rad17 and -9) accumulate in subchromatin microcompartments delineated by single-stranded DNA (ssDNA). BRCA1 and the Mre11–Rad50–Nbs1 complex interact with both of these compartments. Importantly, some core DSB regulators do not form cytologically discernible foci. These are further subclassified to proteins that connect DSBs with the rest of the nucleus (Chk1 and -2), that assemble at unprocessed DSBs (DNA-PK/Ku70), and that exist on chromatin as preassembled complexes but become locally modified after DNA damage (Smc1/Smc3). Finally, checkpoint effectors such as p53 and Cdc25A do not accumulate at DSBs at all. We propose that subclassification of DSB regulators according to their residence sites provides a useful framework for understanding their involvement in diverse processes of genome surveillance.
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spelling pubmed-20638112007-11-29 Spatial organization of the mammalian genome surveillance machinery in response to DNA strand breaks Bekker-Jensen, Simon Lukas, Claudia Kitagawa, Risa Melander, Fredrik Kastan, Michael B. Bartek, Jiri Lukas, Jiri J Cell Biol Research Articles We show that DNA double-strand breaks (DSBs) induce complex subcompartmentalization of genome surveillance regulators. Chromatin marked by γ-H2AX is occupied by ataxia telangiectasia–mutated (ATM) kinase, Mdc1, and 53BP1. In contrast, repair factors (Rad51, Rad52, BRCA2, and FANCD2), ATM and Rad-3–related (ATR) cascade (ATR, ATR interacting protein, and replication protein A), and the DNA clamp (Rad17 and -9) accumulate in subchromatin microcompartments delineated by single-stranded DNA (ssDNA). BRCA1 and the Mre11–Rad50–Nbs1 complex interact with both of these compartments. Importantly, some core DSB regulators do not form cytologically discernible foci. These are further subclassified to proteins that connect DSBs with the rest of the nucleus (Chk1 and -2), that assemble at unprocessed DSBs (DNA-PK/Ku70), and that exist on chromatin as preassembled complexes but become locally modified after DNA damage (Smc1/Smc3). Finally, checkpoint effectors such as p53 and Cdc25A do not accumulate at DSBs at all. We propose that subclassification of DSB regulators according to their residence sites provides a useful framework for understanding their involvement in diverse processes of genome surveillance. The Rockefeller University Press 2006-04-24 /pmc/articles/PMC2063811/ /pubmed/16618811 http://dx.doi.org/10.1083/jcb.200510130 Text en Copyright © 2006, 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
Bekker-Jensen, Simon
Lukas, Claudia
Kitagawa, Risa
Melander, Fredrik
Kastan, Michael B.
Bartek, Jiri
Lukas, Jiri
Spatial organization of the mammalian genome surveillance machinery in response to DNA strand breaks
title Spatial organization of the mammalian genome surveillance machinery in response to DNA strand breaks
title_full Spatial organization of the mammalian genome surveillance machinery in response to DNA strand breaks
title_fullStr Spatial organization of the mammalian genome surveillance machinery in response to DNA strand breaks
title_full_unstemmed Spatial organization of the mammalian genome surveillance machinery in response to DNA strand breaks
title_short Spatial organization of the mammalian genome surveillance machinery in response to DNA strand breaks
title_sort spatial organization of the mammalian genome surveillance machinery in response to dna strand breaks
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2063811/
https://www.ncbi.nlm.nih.gov/pubmed/16618811
http://dx.doi.org/10.1083/jcb.200510130
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