摘要：SummaryChemical modifications and adducts at DNA double-strand break (DSB) ends must be cleaned before re-joining by non-homologous end-joining (NHEJ). MRE11 nuclease is essential for efficient removal of Topoisomerase II (TOP2)-DNA adducts from TOP2 poison-induced DSBs. However, mechanisms in MRE11 recruitment to DSB sites in G1phase remain poorly understood. Here, we report that TOP2-DNA adducts are expeditiously removed through UBC13-mediated polyubiquitination, which promotes DSB resection in G2phase. We found that this ubiquitin signaling is required for efficient recruitment of MRE11 onto DSB sites in G1by facilitating localization of RAP80 and BRCA1 to DSB sites and complex formation between BRCA1 and MRE11 at DSB sites. UBC13 and MRE11 are dispensable for restriction-enzyme-induced “clean” DSBs repair but responsible for over 50% and 70% of NHEJ-dependent repair of γ-ray-induced “dirty” DSBs, respectively. In conclusion, ubiquitin signaling promotes nucleolytic removal of DSB blocking adducts by MRE11 before NHEJ.Graphical AbstractDisplay OmittedHighlights•We establish a bioassay to identify the proteins that remove blocking adducts•UBC13 facilitates the removal of blocking adducts by recruiting MRE11 to DSB sites•UBC13 and RAP80 are required for BRCA1-MRE11 interaction in G1phase•The UBC13-BRCA1-MRE11 axis functions independently of TDP2Biological Sciences; Molecular Biology; Cell Biology
