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タイトル: | Smarcal1 promotes double-strand-break repair by nonhomologous end-joining. |
著者: | Keka, Islam Shamima Mohiuddin Maede, Yuko Rahman, Md Maminur Sakuma, Tetsushi Honma, Masamitsu Yamamoto, Takashi Takeda, Shunichi Sasanuma, Hiroyuki |
著者名の別形: | 本間, 正充 山本, 卓 武田, 俊一 笹沼, 博之 |
発行日: | 18-Jun-2015 |
出版者: | Oxford University Press |
誌名: | Nucleic acids research |
巻: | 43 |
号: | 13 |
終了ページ: | 6359 |
論文番号: | 6372 |
抄録: | Smarcal1 is a SWI/SNF-family protein with an ATPase domain involved in DNA-annealing activities and a binding site for the RPA single-strand-DNA-binding protein. Although the role played by Smarcal1 in the maintenance of replication forks has been established, it remains unknown whether Smarcal1 contributes to genomic DNA maintenance outside of the S phase. We disrupted the SMARCAL1 gene in both the chicken DT40 and the human TK6 B cell lines. The resulting SMARCAL1(-/-) clones exhibited sensitivity to chemotherapeutic topoisomerase 2 inhibitors, just as nonhomologous end-joining (NHEJ) null-deficient cells do. SMARCAL1(-/-) cells also exhibited an increase in radiosensitivity in the G1 phase. Moreover, the loss of Smarcal1 in NHEJ null-deficient cells does not further increase their radiosensitivity. These results demonstrate that Smarcal1 is required for efficient NHEJ-mediated DSB repair. Both inactivation of the ATPase domain and deletion of the RPA-binding site cause the same phenotype as does null-mutation of Smarcal1, suggesting that Smarcal1 enhances NHEJ, presumably by interacting with RPA at unwound single-strand sequences and then facilitating annealing at DSB ends. SMARCAL1(-/-)cells showed a poor accumulation of Ku70/DNA-PKcs and XRCC4 at DNA-damage sites. We propose that Smarcal1 maintains the duplex status of DSBs to ensure proper recruitment of NHEJ factors to DSB sites. |
記述: | シムケ免疫不全・骨形成不全症の原因遺伝子SMARCAL1は、DNA二重鎖切断損傷からゲノムを守る. 京都大学プレスリリース. 2015-06-23. |
著作権等: | © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
URI: | http://hdl.handle.net/2433/198501 |
DOI(出版社版): | 10.1093/nar/gkv621 |
PubMed ID: | 26089390 |
関連リンク: | https://www.kyoto-u.ac.jp/ja/research-news/2015-06-23 |
出現コレクション: | 学術雑誌掲載論文等 |
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