RIF1 suppresses the formation of single-stranded ultrafine anaphase bridges via protein phosphatase 1.

Resolution of ultrafine anaphase bridges (UFBs) must be completed before cytokinesis to ensure sister-chromatid disjunction. RIF1 is involved in UFB resolution by a mechanism that is not yet clear. Here, we show that RIF1 functions in mitosis to inhibit the formation of 53BP1 nuclear bodies and micronuclei. Meanwhile, RIF1 localizes on PICH-coated double-stranded UFBs but not on RPA-coated single-stranded UFBs. Depletion of RIF1 leads to an elevated level of RPA-coated UFBs, in a BLM-dependent manner. RIF1 interacts with all three isoforms of protein phosphatase 1 (PP1) at its CI domain in anaphase when CDK1 activity declines. CDK1 negatively regulates RIF1-PP1 interaction via the CIII domain of RIF1. Importantly, depletion of PP1 phenocopies RIF1 depletion, and phosphorylation-resistant mutant of PICH shows reduced interaction with the BTR complex and bypasses the need of RIF1 in preventing the formation of single-stranded UFBs. Overall, our data show that PP1 is the effector of RIF1 in UFB resolution.