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Nucleolin Participates in DNA Double-Strand Break-Induced Damage Response through MDC1-Dependent Pathway
H2AX is an important factor for chromatin remodeling to facilitate accumulation of DNA damage-related proteins at DNA double-strand break (DSB) sites. In order to further understand the role of H2AX in the DNA damage response (DDR), we attempted to identify H2AX-interacting proteins by proteomics an...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3492271/ https://www.ncbi.nlm.nih.gov/pubmed/23145133 http://dx.doi.org/10.1371/journal.pone.0049245 |
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author | Kobayashi, Junya Fujimoto, Hiroko Sato, Jun Hayashi, Ikue Burma, Sandeep Matsuura, Shinya Chen, David J. Komatsu, Kenshi |
author_facet | Kobayashi, Junya Fujimoto, Hiroko Sato, Jun Hayashi, Ikue Burma, Sandeep Matsuura, Shinya Chen, David J. Komatsu, Kenshi |
author_sort | Kobayashi, Junya |
collection | PubMed |
description | H2AX is an important factor for chromatin remodeling to facilitate accumulation of DNA damage-related proteins at DNA double-strand break (DSB) sites. In order to further understand the role of H2AX in the DNA damage response (DDR), we attempted to identify H2AX-interacting proteins by proteomics analysis. As a result, we identified nucleolin as one of candidates. Here, we show a novel role of a major nucleolar protein, nucleolin, in DDR. Nucleolin interacted with γ-H2AX and accumulated to laser micro-irradiated DSB damage sites. Chromatin Immunoprecipitation assay also displayed the accumulation of nucleolin around DSB sites. Nucleolin-depleted cells exhibited repression of both ATM-dependent phosphorylation following exposure to γ-ray and subsequent cell cycle checkpoint activation. Furthermore, nucleolin-knockdown reduced HR and NHEJ activity and showed decrease in IR-induced chromatin accumulation of HR/NHEJ factors, agreeing with the delayed kinetics of γ-H2AX focus. Moreover, nucleolin-knockdown decreased MDC1-related events such as focus formation of 53 BP1, RNF168, phosphorylated ATM, and H2A ubiquitination. Nucleolin also showed FACT-like activity for DSB damage-induced histone eviction from chromatin. Taken together, nucleolin could promote both ATM-dependent cell cycle checkpoint and DSB repair by functioning in an MDC1-related pathway through its FACT-like function. |
format | Online Article Text |
id | pubmed-3492271 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-34922712012-11-09 Nucleolin Participates in DNA Double-Strand Break-Induced Damage Response through MDC1-Dependent Pathway Kobayashi, Junya Fujimoto, Hiroko Sato, Jun Hayashi, Ikue Burma, Sandeep Matsuura, Shinya Chen, David J. Komatsu, Kenshi PLoS One Research Article H2AX is an important factor for chromatin remodeling to facilitate accumulation of DNA damage-related proteins at DNA double-strand break (DSB) sites. In order to further understand the role of H2AX in the DNA damage response (DDR), we attempted to identify H2AX-interacting proteins by proteomics analysis. As a result, we identified nucleolin as one of candidates. Here, we show a novel role of a major nucleolar protein, nucleolin, in DDR. Nucleolin interacted with γ-H2AX and accumulated to laser micro-irradiated DSB damage sites. Chromatin Immunoprecipitation assay also displayed the accumulation of nucleolin around DSB sites. Nucleolin-depleted cells exhibited repression of both ATM-dependent phosphorylation following exposure to γ-ray and subsequent cell cycle checkpoint activation. Furthermore, nucleolin-knockdown reduced HR and NHEJ activity and showed decrease in IR-induced chromatin accumulation of HR/NHEJ factors, agreeing with the delayed kinetics of γ-H2AX focus. Moreover, nucleolin-knockdown decreased MDC1-related events such as focus formation of 53 BP1, RNF168, phosphorylated ATM, and H2A ubiquitination. Nucleolin also showed FACT-like activity for DSB damage-induced histone eviction from chromatin. Taken together, nucleolin could promote both ATM-dependent cell cycle checkpoint and DSB repair by functioning in an MDC1-related pathway through its FACT-like function. Public Library of Science 2012-11-07 /pmc/articles/PMC3492271/ /pubmed/23145133 http://dx.doi.org/10.1371/journal.pone.0049245 Text en © 2012 Kobayashi et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Kobayashi, Junya Fujimoto, Hiroko Sato, Jun Hayashi, Ikue Burma, Sandeep Matsuura, Shinya Chen, David J. Komatsu, Kenshi Nucleolin Participates in DNA Double-Strand Break-Induced Damage Response through MDC1-Dependent Pathway |
title | Nucleolin Participates in DNA Double-Strand Break-Induced Damage Response through MDC1-Dependent Pathway |
title_full | Nucleolin Participates in DNA Double-Strand Break-Induced Damage Response through MDC1-Dependent Pathway |
title_fullStr | Nucleolin Participates in DNA Double-Strand Break-Induced Damage Response through MDC1-Dependent Pathway |
title_full_unstemmed | Nucleolin Participates in DNA Double-Strand Break-Induced Damage Response through MDC1-Dependent Pathway |
title_short | Nucleolin Participates in DNA Double-Strand Break-Induced Damage Response through MDC1-Dependent Pathway |
title_sort | nucleolin participates in dna double-strand break-induced damage response through mdc1-dependent pathway |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3492271/ https://www.ncbi.nlm.nih.gov/pubmed/23145133 http://dx.doi.org/10.1371/journal.pone.0049245 |
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