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- W3014353722 endingPage "101027" @default.
- W3014353722 startingPage "101027" @default.
- W3014353722 abstract "Chemical 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 G1 phase remain poorly understood. Here, we report that TOP2-DNA adducts are expeditiously removed through UBC13-mediated polyubiquitination, which promotes DSB resection in G2 phase. We found that this ubiquitin signaling is required for efficient recruitment of MRE11 onto DSB sites in G1 by 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." @default.
- W3014353722 created "2020-04-10" @default.
- W3014353722 creator A5020161951 @default.
- W3014353722 creator A5033818746 @default.
- W3014353722 creator A5038271827 @default.
- W3014353722 creator A5038682900 @default.
- W3014353722 creator A5066235441 @default.
- W3014353722 creator A5070076495 @default.
- W3014353722 creator A5072036205 @default.
- W3014353722 creator A5073128750 @default.
- W3014353722 creator A5081596830 @default.
- W3014353722 creator A5084940370 @default.
- W3014353722 creator A5086435305 @default.
- W3014353722 date "2020-04-01" @default.
- W3014353722 modified "2023-10-16" @default.
- W3014353722 title "UBC13-Mediated Ubiquitin Signaling Promotes Removal of Blocking Adducts from DNA Double-Strand Breaks" @default.
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