The RSF1 histone-remodelling factor facilitates DNA double-strand break repair by recruiting centromeric and Fanconi Anaemia proteins.

ATM is a central regulator of the cellular responses to DNA double-strand breaks (DSBs). Here we identify a biochemical interaction between ATM and RSF1 and we characterise the role of RSF1 in this response. The ATM-RSF1 interaction is dependent upon both DSBs and ATM kinase activity. Together with SNF2H/SMARCA5, RSF1 ...
forms the RSF chromatin-remodelling complex. Although RSF1 is specific to the RSF complex, SNF2H/SMARCA5 is a catalytic subunit of several other chromatin-remodelling complexes. Although not required for checkpoint signalling, RSF1 is required for efficient repair of DSBs via both end-joining and homology-directed repair. Specifically, the ATM-dependent recruitment to sites of DSBs of the histone fold proteins CENPS/MHF1 and CENPX/MHF2, previously identified at centromeres, is RSF1-dependent. In turn these proteins recruit and regulate the mono-ubiquitination of the Fanconi Anaemia proteins FANCD2 and FANCI. We propose that by depositing CENPS/MHF1 and CENPX/MHF2, the RSF complex either directly or indirectly contributes to the reorganisation of chromatin around DSBs that is required for efficient DNA repair.
Mesh Terms:
Adenosine Triphosphatases, Animals, Ataxia Telangiectasia Mutated Proteins, B-Lymphocytes, Cell Line, Tumor, Chickens, Chromatin, Chromosomal Proteins, Non-Histone, DNA, DNA Breaks, Double-Stranded, DNA End-Joining Repair, DNA-Binding Proteins, Epithelial Cells, Fanconi Anemia Complementation Group D2 Protein, Fanconi Anemia Complementation Group Proteins, Gene Expression Regulation, Histones, Humans, Nuclear Proteins, Recombinational DNA Repair, Signal Transduction, Trans-Activators
PLoS Biol.
Date: May. 01, 2014
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