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- W2754791657 endingPage "11781" @default.
- W2754791657 startingPage "11766" @default.
- W2754791657 abstract "Nucleolytic resection of DNA double-strand breaks (DSBs) is essential for both checkpoint activation and homology-mediated repair; however, the precise mechanism of resection, especially the initiation step, remains incompletely understood. Resection of blocked ends with protein or chemical adducts is believed to be initiated by the MRN complex in conjunction with CtIP through internal cleavage of the 5' strand DNA. However, it is not clear whether resection of clean DSBs with free ends is also initiated by the same mechanism. Using the Xenopus nuclear extract system, here we show that the Dna2 nuclease directly initiates the resection of clean DSBs by cleaving the 5' strand DNA ∼10-20 nucleotides away from the ends. In the absence of Dna2, MRN together with CtIP mediate an alternative resection initiation pathway where the nuclease activity of MRN apparently directly cleaves the 5' strand DNA at more distal sites. MRN also facilitates resection initiation by promoting the recruitment of Dna2 and CtIP to the DNA substrate. The ssDNA-binding protein RPA promotes both Dna2- and CtIP-MRN-dependent resection initiation, but a RPA mutant can distinguish between these pathways. Our results strongly suggest that resection of blocked and clean DSBs is initiated via distinct mechanisms." @default.
- W2754791657 created "2017-09-25" @default.
- W2754791657 creator A5009985634 @default.
- W2754791657 creator A5010612497 @default.
- W2754791657 creator A5015025705 @default.
- W2754791657 creator A5074860235 @default.
- W2754791657 creator A5090074105 @default.
- W2754791657 date "2017-09-14" @default.
- W2754791657 modified "2023-09-27" @default.
- W2754791657 title "Dna2 initiates resection at clean DNA double-strand breaks" @default.
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