ALC1/CHD1L, chromatin-remodeling enzyme, is required for efficient base excision repair
PLoS ONE 12 巻 11 号
e0188320- 頁
2017-11-17 発行
アクセス数 : 469 件
ダウンロード数 : 91 件
今月のアクセス数 : 2 件
今月のダウンロード数 : 2 件
この文献の参照には次のURLをご利用ください : https://ir.lib.hiroshima-u.ac.jp/00048693
| ファイル情報(添付) | |
| タイトル ( eng ) |
ALC1/CHD1L, chromatin-remodeling enzyme, is required for efficient base excision repair
|
| 作成者 |
Cho Kosai
Ooka Masato
Shimizu Naoto
Watanabe Reiko
Yasui Akira
Nakazawa Yuka
Ogi Tomoo
Harada Hiroshi
Agama Keli
Nakamura Jun
Asada Ryuta
Fujiike Haruna
Murai Junko
Hiraoka Masahiro
Koike Kaoru
Pommier Yves
Takeda Shunichi
Hirota Kouji
|
| 収録物名 |
PLoS ONE
|
| 巻 | 12 |
| 号 | 11 |
| 開始ページ | e0188320 |
| 抄録 |
ALC1/CHD1L is a member of the SNF2 superfamily of ATPases carrying a macrodomain that binds poly(ADP-ribose). Poly(ADP-ribose) polymerase (PARP) 1 and 2 synthesize poly(ADP-ribose) at DNA-strand cleavage sites, promoting base excision repair (BER). Although depletion of ALC1 causes increased sensitivity to various DNA-damaging agents (H2O2, UV, and phleomycin), the role played by ALC1 in BER has not yet been established. To explore this role, as well as the role of ALC1’s ATPase activity in BER, we disrupted the ALC1 gene and inserted the ATPase-dead (E165Q) mutation into the ALC1 gene in chicken DT40 cells, which do not express PARP2. The resulting ALC1-/- and ALC1-/E165Q cells displayed an indistinguishable hypersensitivity to methylmethane sulfonate (MMS), an alkylating agent, and to H2O2, indicating that ATPase plays an essential role in the DNA-damage response. PARP1-/- and ALC1-/-/PARP1-/- cells exhibited a very similar sensitivity to MMS, suggesting that ALC1 and PARP1 collaborate in BER. Following pulse-exposure to H2O2, PARP1-/- and ALC1-/-/PARP1-/- cells showed similarly delayed kinetics in the repair of single-strand breaks, which arise as BER intermediates. To ascertain ALC1’s role in BER in mammalian cells, we disrupted the ALC1 gene in human TK6 cells. Following exposure to MMS and to H2O2, the ALC1-/- TK6 cell line showed a delay in single-strand-break repair. We therefore conclude that ALC1 plays a role in BER. Following exposure to H2O2, ALC1-/- cells showed compromised chromatin relaxation. We thus propose that ALC1 is a unique BER factor that functions in a chromatin context, most likely as a chromatin-remodeling enzyme.
|
| 内容記述 |
This work was supported by the JSPS KAKENHI Grant Number (JP16K12598, JP16H02957 and JP16H01314 to KH, JP16H06306 to ST and JP16J02252 to RA), the JSPS Core-to-Core Program (A) Advanced Research Networks (to ST), the Takeda Science Foundation and Yamada Science Foundation (to KH), and the Center for Cancer Research, Intramural Program of the US National Cancer Institute (Z01 BC 006150 to KA and YP). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
|
| 言語 |
英語
|
| 資源タイプ | 学術雑誌論文 |
| 出版者 |
Public Library of Science
|
| 発行日 | 2017-11-17 |
| 権利情報 |
This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
|
| 出版タイプ | Version of Record（出版社版。早期公開を含む） |
| アクセス権 | オープンアクセス |
| 収録物識別子 |
[DOI] 10.1371/journal.pone.0188320
[DOI] https://doi.org/10.1371/journal.pone.0188320
[ISSN] 1932-6203
[PMID] 29149203
|
