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. © 2014 pessina,lowndes.