
효모 Saccharomyces cerevisiae Rev7는 Mre11 핵산분해 활성과 Rad50 ATPase 활성을 직접 결합하고 차단함으로써 DSB 수리 경로 선택을 조절한다.


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Recent studies in cancer cell lines have shown that the tetrameric Shieldin complex (comprising REV7, SHLD1, SHLD2, and SHLD3) facilitates non-homologous end-joining (NHEJ), while blocking homologous recombination (HR). Surprisingly, several eukaryotic species lack SHLD1, SHLD2 and SHLD3 orthologs, suggesting that Rev7 may leverage an alternative mechanism to regulate the double-strand break (DSB) repair pathway choice. Exploring this hypothesis, we discovered that Saccharomyces cerevisiae Rev7 robustly interacts with the Mre11-Rad50-Xrs2 (MRX) subunits, impedes G-quadruplex DNA synergised, HU-induced toxicity and facilitates NHEJ, while antagonizing HR. We identified a 42-aminoacid C-terminal fragment of Rev7 that was critical for its binding to the subunits of MRX complex, protect rev7Δ cells from G-quadruplex DNA-HU-induced toxicity and promote NHEJ by inhibiting HR, whereas the N-terminal HORMA domain, a conserved protein–protein interaction module, was dispensable. We further demonstrate that the full-length Rev7 impedes Mre11 nuclease and Rad50’s ATPase activities, without affecting the latter’s ATP-binding ability. Notably, we found that Rev7 binds with high affinity and specificity to G-quadruplex structures, as opposed to no binding to mixed-sequence single- and double-stranded DNA. These data uncover unanticipated insights into the functional interaction between the MRX subunits and Rev7, and highlight a mechanism by which it regulates the DSB repair pathway choice between HR and NHEJ in S. cerevisiae .

### Competing Interest Statement

The authors have declared no competing interest.

Saccharomyces cerevisiae Rev7 regulates DSB repair pathway choice through binding and blocking Mre11 nuclease and Rad50 ATPase activities

효모-saccharomyces-cerevisiae-rev7가-mre11-핵산분해-활성과-rad50-atpase-활성을-결합하고-차단함으로써-dsb-수리-경로-선택을-조절한다


효모 Saccharomyces cerevisiae Rev7가 Mre11 핵산분해 활성과 Rad50 ATPase 활성을 결합하고 차단함으로써 DSB 수리 경로 선택을 조절한다
