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| Title: | Nucleolin Participates in DNA Double-Strand Break-Induced Damage Response through MDC1-Dependent Pathway. |
| Authors: | Kobayashi, Junya
Fujimoto, Hiroko
Sato, Jun
Hayashi, Ikue
Burma, Sandeep
Matsuura, Shinya
Chen, David J
Komatsu, Kenshi |
| Author's alias: | 小林, 純也 |
| Issue Date: | 7-Nov-2012 |
| Journal title: | PloS one |
| Volume: | 7 |
| Issue: | 11 |
| Thesis number: | e49245 |
| DOI: | 10.1371/journal.pone.0049245 |
| Abstract: | 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. |
| Rights: | © 2012 Kobayashi et al. 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 credited. |
| URI: | http://hdl.handle.net/2433/162961 |
| PubMed ID: | 23145133 |
| Appears in Collections: | Journal Articles |
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