Molecular Cell
Volume 40, Issue 6, 22 December 2010, Pages 976-987
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Article
The ACF1 Complex Is Required for DNA Double-Strand Break Repair in Human Cells

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Summary

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.

Highlights

► ATP-dependent chromatin-remodeling complex, CHRAC, is required for NHEJ and HR ► ACF1 is required for the accumulation of KU proteins at DNA double-strand breaks ► KU70 interacts with ACF1, and KU complex with CHRAC, in a DSB-dependent manner ► NHEJ proteins and remodeling factors were visualized at nuclease-induced DSBs

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Present address: Department of Microbiology and Molecular Genetics, School of Medicine, University of Pittsburgh, Hillman Cancer Center, Research Pavilion, Suite 2.6, 5117 Centre Avenue, Pittsburgh, PA 15213, USA