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Cell Cycle. 2014;13(4):666-77. doi: 10.4161/cc.27548. Epub 2013 Dec 18.

ATM-dependent chromatin remodeler Rsf-1 facilitates DNA damage checkpoints and homologous recombination repair.

Author information

  • 1Department of Biochemistry; Ajou University School of Medicine; Suwon, South Korea; Genomic Instability Research Center; Ajou University School of Medicine; Suwon, South Korea.
  • 2Department of Biochemistry; Ajou University School of Medicine; Suwon, South Korea.
  • 3Department of Life Science; College of Natural Sciences; Ajou University; Suwon, South Korea.
  • 4Genomic Instability Research Center; Ajou University School of Medicine; Suwon, South Korea.

Abstract

As a member of imitation switch (ISWI) family in ATP-dependent chromatin remodeling factors, RSF complex consists of SNF2h ATPase and Rsf-1. Although it has been reported that SNF2h ATPase is recruited to DNA damage sites (DSBs) in a poly(ADP-ribosyl) polymerase 1 (PARP1)-dependent manner in DNA damage response (DDR), the function of Rsf-1 is still elusive. Here we show that Rsf-1 is recruited to DSBs confirmed by various cellular analyses. Moreover, the initial recruitment of Rsf-1 and SNF2h to DSBs shows faster kinetics than that of γH2AX after micro-irradiation. Signals of Rsf-1 and SNF2h are retained over 30 min after micro-irradiation, whereas γH2AX signals are gradually reduced at 10 min. In addition, Rsf-1 is accumulated at DSBs in ATM-dependent manner, and the putative pSQ motifs of Rsf-1 by ATM are required for its accumulation at DSBs. Furtheremore, depletion of Rsf-1 attenuates the activation of DNA damage checkpoint signals and cell survival upon DNA damage. Finally, we demonstrate that Rsf-1 promotes homologous recombination repair (HRR) by recruiting resection factors RPA32 and Rad51. Thus, these findings reveal a new function of chromatin remodeler Rsf-1 as a guard in DNA damage checkpoints and homologous recombination repair.

KEYWORDS:

ATM; DNA damage checkpoints; DNA double-strand breaks; ISWI chromatin remodeler; Rsf-1; homologous recombination repair

PMID:
24351651
DOI:
10.4161/cc.27548
[PubMed - indexed for MEDLINE]
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