BRG1 promotes the repair of DNA double-strand breaks by facilitating the replacement of RPA with RAD51.
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 DSB-induced 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.
The Key Laboratory of Molecular Epigenetics of MOE, Institute of Genetics and Cytology, School of Life Sciences, Northeast Normal University, #5268, Renmin Street, Changchun, Jilin, 130024, China.
Wenjing
W
Qi
The Key Laboratory of Molecular Epigenetics of MOE, Institute of Genetics and Cytology, School of Life Sciences, Northeast Normal University, #5268, Renmin Street, Changchun, Jilin, 130024, China.
Ruoxi
R
Wang
The Key Laboratory of Molecular Epigenetics of MOE, Institute of Genetics and Cytology, School of Life Sciences, Northeast Normal University, #5268, Renmin Street, Changchun, Jilin, 130024, China.
Hongyu
H
Chen
The Key Laboratory of Molecular Epigenetics of MOE, Institute of Genetics and Cytology, School of Life Sciences, Northeast Normal University, #5268, Renmin Street, Changchun, Jilin, 130024, China.
Xiaolin
X
Wang
The Key Laboratory of Molecular Epigenetics of MOE, Institute of Genetics and Cytology, School of Life Sciences, Northeast Normal University, #5268, Renmin Street, Changchun, Jilin, 130024, China.
Ting
T
Xiao
Department of Microbiology and Immunology, Sealy Center for Molecular Medicine, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA.
Istvan
I
Boldogh
The Key Laboratory of Molecular Epigenetics of MOE, Institute of Genetics and Cytology, School of Life Sciences, Northeast Normal University, #5268, Renmin Street, Changchun, Jilin, 130024, China baxq755@nenu.edu.cn zengx779@nenu.edu.cn.
Xueqing
X
Ba
Department of Bioscience, Changchun Normal University, #677, Changji Northroad, Changchun, Jilin, 130032, China.
Liping
L
Han
The Key Laboratory of Molecular Epigenetics of MOE, Institute of Genetics and Cytology, School of Life Sciences, Northeast Normal University, #5268, Renmin Street, Changchun, Jilin, 130024, China baxq755@nenu.edu.cn zengx779@nenu.edu.cn.
Xianlu
X
Zeng
D002460:Cell Line; D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects / Q000235:genetics; D059766:DNA End-Joining Repair / Q000235:genetics*; D004265:DNA Helicases / Q000096:biosynthesis / Q000235:genetics*; D004277:DNA, Single-Stranded / Q000187:drug effects / Q000235:genetics; D005047:Etoposide / Q000633:toxicity; D042822:Genomic Instability; D059765:Homologous Recombination / Q000235:genetics; D006801:Humans; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D051135:Rad51 Recombinase / Q000096:biosynthesis / Q000235:genetics*; D051721:Rad52 DNA Repair and Recombination Protein / Q000235:genetics*; D051716:Replication Protein A / Q000235:genetics*; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*
D004277:DNA, Single-Stranded; D009687:Nuclear Proteins; C497194:RAD52 protein, human; C497167:RPA1 protein, human; D051721:Rad52 DNA Repair and Recombination Protein; D051716:Replication Protein A; D014157:Transcription Factors; D005047:Etoposide; D051135:Rad51 Recombinase; C084108:SMARCA4 protein, human; D004265:DNA Helicases
BRG1; DNA double-strand break; Homologous recombination; RAD51; RAD52