BRG1 promotes the repair of DNA double-strand breaks by facilitating the replacement of RPA with RAD51

Wenjing Qi, Ruoxi Wang, Hongyu Chen, Xiaolin Wang, Ting Xiao, Istvan Boldogh, Xueqing Ba, Liping Han, Xianlu Zeng

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

DNA double-strand breaks (DSBs) are a type of lethal DNA damage. The repair of DSBs requires tight coordination between the factors modulating chromatin structure and the DNA repair machinery. BRG1, the ATPase subunit of the chromatin remodelling complex Switch/Sucrose non-fermentable (SWI/SNF), is often linked to tumorigenesis and genome instability, and its role in DSB repair remains largely unclear. In the present study, we show that BRG1 is recruited to DSB sites and enhances DSB repair. Using DR-GFP and EJ5-GFP reporter systems, we demonstrate that BRG1 facilitates homologous recombination repair rather than nonhomologous end-joining (NHEJ) repair. Moreover, the BRG1- RAD52 complex mediates the replacement of RPA with RAD51 on single-stranded DNA (ssDNA) to initiate DNA strand invasion. Loss of BRG1 results in a failure of RAD51 loading onto ssDNA, abnormal homologous recombination repair and enhanced DSBinduced lethality. Our present study provides a mechanistic insight into how BRG1, which is known to be involved in chromatin remodelling, plays a substantial role in the homologous recombination repair pathway in mammalian cells.

Original languageEnglish (US)
Pages (from-to)317-330
Number of pages14
JournalJournal of Cell Science
Volume128
Issue number2
DOIs
StatePublished - 2015

Fingerprint

Recombinational DNA Repair
Double-Stranded DNA Breaks
Chromatin Assembly and Disassembly
Single-Stranded DNA
Switch Genes
Genomic Instability
DNA Repair
DNA Damage
Chromatin
Adenosine Triphosphatases
Sucrose
Carcinogenesis
DNA

Keywords

  • BRG1
  • DNA double-strand break
  • Homologous recombination
  • RAD51
  • RAD52

ASJC Scopus subject areas

  • Cell Biology

Cite this

BRG1 promotes the repair of DNA double-strand breaks by facilitating the replacement of RPA with RAD51. / Qi, Wenjing; Wang, Ruoxi; Chen, Hongyu; Wang, Xiaolin; Xiao, Ting; Boldogh, Istvan; Ba, Xueqing; Han, Liping; Zeng, Xianlu.

In: Journal of Cell Science, Vol. 128, No. 2, 2015, p. 317-330.

Research output: Contribution to journalArticle

Qi, Wenjing ; Wang, Ruoxi ; Chen, Hongyu ; Wang, Xiaolin ; Xiao, Ting ; Boldogh, Istvan ; Ba, Xueqing ; Han, Liping ; Zeng, Xianlu. / BRG1 promotes the repair of DNA double-strand breaks by facilitating the replacement of RPA with RAD51. In: Journal of Cell Science. 2015 ; Vol. 128, No. 2. pp. 317-330.
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