Nature Communications · 2017 · 26 citations · 51 references
Life SciencesCell BiologyMolecular BiologyCell DivisionChromatin BiologyDna RepairDna Damage SignalingDna Double-strand Break RepairDouble-strand Break RepairHomologous RecombinationNon-homologous End JoiningRepair Pathway ChoiceChk1 SignalingDna Damage Repair PathwaysDna Double-strand Break Repair Pathway ChoiceDouble-strand Break Repair PathwaysNon-homologous End Joining SignalingPathway Choice After Double-strand BreaksS/g2 TransitionUbiquitin Binding
Abstract Double-strand breaks (DSBs) are repaired through two major pathways, homology-directed recombination (HDR) and non-homologous end joining (NHEJ). While HDR can only occur in S/G2, NHEJ can happen in all cell cycle phases (except mitosis). How then is the repair choice made in S/G2 cells? Here we provide evidence demonstrating that APC Cdh1 plays a critical role in choosing the repair pathways in S/G2 cells. Our results suggest that the default for all DSBs is to recruit 53BP1 and RIF1. BRCA1 is blocked from being recruited to broken ends because its recruitment signal, K63-linked poly-ubiquitin chains on histones, is actively destroyed by the deubiquitinating enzyme USP1. We show that the removal of USP1 depends on APC Cdh1 and requires Chk1 activation known to be catalysed by ssDNA-RPA-ATR signalling at the ends designated for HDR, linking the status of end processing to RIF1 or BRCA1 recruitment.
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Sensing DNA Damage Through ATRIP Recognition of RPA-ssDNA Complexes
Lee Zou, Stephen J. Elledge · Science · 2003 · 2.7K citations
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Ralph Scully, Junjie Chen, Robert Ochs et al. · Cell · 1997 · 909 citations · Full text