Fig. 7: Model of suppression of BRCA1-dependent resection by the RIF1–ASF1 complex.
From: RIF1-ASF1-mediated high-order chromatin structure safeguards genome integrity

DSB ends are recognized and bound by Ku, which prevents directly resection by EXO1 or DNA2/BLM. 53BP1 binds to adjacent chromatin and recruits the RIF1–ASF1 complex, which provides H3–H4 heterodimers with K9me1 on H3 for nucleosome assembly/exchange. SUV39h1/2 then converts H3K9me1 to H3K9me3, which recruits HP1, leading to heterochromatinization. Chromatin condensation by heterochromatinization suppresses CtIP-MRN-mediated initiation of resection, and inhibits microhomology-mediated end joining (MMEJ), HR, and SSA. When NHEJ repair does not ensue, 53BP1 and the RIF1–ASF1 complex will be excluded from the chromatin proximal to the breaks by BRCA1 for initiating resection, but will retain at the distal chromatin to restrict resection and prevent SSA.