TY - JOUR
T1 - The ACF1 Complex Is Required for DNA Double-Strand Break Repair in Human Cells
AU - Lan, Li
AU - Ui, Ayako
AU - Nakajima, Satoshi
AU - Hatakeyama, Kotomi
AU - Hoshi, Mikiko
AU - Watanabe, Reiko
AU - Janicki, Susan M.
AU - Ogiwara, Hideaki
AU - Kohno, Takashi
AU - Kanno, Shin ichiro
AU - Yasui, Akira
N1 - Funding Information:
We thank Drs. Patrick Varga-Weisz, David Chen, Maria Jasin, and Kenshi Komatsu for providing experimental materials; Dr. Tsutomu Shimura for advice on the comet assay; Mr. Youhei Satou and Mr. Hiroyuki Kuzuoka for initial contributions to the work; Dr. Shirley McCready for editing the paper; and Dr. Yuuki Murakami for experimental assistance. We also thank Dr. Samuel Wilson for discussion of the manuscript. This work was funded with the Grants-in-Aid for Scientific Research and from the Ministry of Education, Culture, Sports, Science and Technology, Japan, to A.Y. (20241011 and 22131005) and S.N. (20710041) and for Cancer Research from the Ministry of Health, Labor and Welfare, Japan, to T.K. (19-9). Postdoctoral grants from JSPS and the grant from Tohoku University for promoting young scientists to L.L. are acknowledged.
PY - 2010/12/22
Y1 - 2010/12/22
N2 - DNA double-strand breaks (DSBs) are repaired via nonhomologous end-joining (NHEJ) or homologous recombination (HR), but cellular repair processes remain elusive. We show here that the ATP-dependent chromatin-remodeling factors, ACF1 and SNF2H, accumulate rapidly at DSBs and are required for DSB repair in human cells. If the expression of ACF1 or SNF2H is suppressed, cells become extremely sensitive to X-rays and chemical treatments producing DSBs, and DSBs remain unrepaired. ACF1 interacts directly with KU70 and is required for the accumulation of KU proteins at DSBs. The KU70/80 complex becomes physically more associated with the chromatin-remodeling factors of the CHRAC complex, which includes ACF1, SNF2H, CHRAC15, and CHRAC17, after treatments producing DSBs. Furthermore, the frequency of NHEJ as well as HR induced by DSBs in chromosomal DNA is significantly decreased in cells depleted of either of these factors. Thus, ACF1 and its complexes play important roles in DSBs repair.
AB - DNA double-strand breaks (DSBs) are repaired via nonhomologous end-joining (NHEJ) or homologous recombination (HR), but cellular repair processes remain elusive. We show here that the ATP-dependent chromatin-remodeling factors, ACF1 and SNF2H, accumulate rapidly at DSBs and are required for DSB repair in human cells. If the expression of ACF1 or SNF2H is suppressed, cells become extremely sensitive to X-rays and chemical treatments producing DSBs, and DSBs remain unrepaired. ACF1 interacts directly with KU70 and is required for the accumulation of KU proteins at DSBs. The KU70/80 complex becomes physically more associated with the chromatin-remodeling factors of the CHRAC complex, which includes ACF1, SNF2H, CHRAC15, and CHRAC17, after treatments producing DSBs. Furthermore, the frequency of NHEJ as well as HR induced by DSBs in chromosomal DNA is significantly decreased in cells depleted of either of these factors. Thus, ACF1 and its complexes play important roles in DSBs repair.
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U2 - 10.1016/j.molcel.2010.12.003
DO - 10.1016/j.molcel.2010.12.003
M3 - Article
C2 - 21172662
AN - SCOPUS:78650238493
SN - 1097-2765
VL - 40
SP - 976
EP - 987
JO - Molecular Cell
JF - Molecular Cell
IS - 6
ER -