期刊
NATURE COMMUNICATIONS
卷 9, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-018-06417-5
关键词
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资金
- Swiss National Science Foundation (SNCF) [31003A_175444, PP00P3_159323]
- European Research Council (ERC) [681630]
- ERC Grant [311336]
- BBSRC grant [BB/M010279/1]
- Royal Society grant [UF110009]
- Wellcome Trust grant [200843/Z/16/Z]
- US National Institute of Health Intramural Program-US National Institute of Environmental Health Sciences (NIEHS) grant [1Z01ES102765]
- Boehringer Ingelheim Fonds PhD fellowship
- Novartis Research Foundation
- Helmut Horten Foundation
- SNSF
- ERC
- ETH Zurich
- Wellcome Trust [200843/Z/16/Z] Funding Source: Wellcome Trust
- BBSRC [BB/M010279/1] Funding Source: UKRI
- MRC [G0800005] Funding Source: UKRI
- Swiss National Science Foundation (SNF) [PP00P3_159323] Funding Source: Swiss National Science Foundation (SNF)
- Royal Society [UF110009] Funding Source: Royal Society
- European Research Council (ERC) [311336] Funding Source: European Research Council (ERC)
DNA end resection plays a critical function in DNA double-strand break repair pathway choice. Resected DNA ends are refractory to end-joining mechanisms and are instead channeled to homology-directed repair. Using biochemical, genetic, and imaging methods, we show that phosphorylation of Saccharomyces cerevisiae Sae2 controls its capacity to promote the Mrell-Rad50-Xrs2 (MRX) nuclease to initiate resection of blocked DNA ends by at least two distinct mechanisms. First, DNA damage and cell cycle-dependent phosphorylation leads to Sae2 tetramerization. Second, and independently, phosphorylation of the conserved C-terminal domain of Sae2 is a prerequisite for its physical interaction with Rad50, which is also crucial to promote the MRX endonuclease. The lack of this interaction explains the phenotype of rad50S mutants defective in the processing of Spoll-bound DNA ends during meiotic recombination. Our results define how phosphorylation controls the initiation of DNA end resection and therefore the choice between the key DNA double-strand break repair mechanisms.
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