期刊
MOLECULAR CELL
卷 60, 期 6, 页码 835-846出版社
CELL PRESS
DOI: 10.1016/j.molcel.2015.10.023
关键词
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资金
- ERC [242928]
- AIRC [IG 14171]
- Fondazione Telethon [GGP12160]
- Ligue contre le Cancer
- ANR
- Region Languedoc-Roussillon (Programme Chercheur d'Avenir)
- ARC
- French Ministry of Research
- Fondation Recherche Medicale
- FIRC fellowship
- European Research Council (ERC) [242928] Funding Source: European Research Council (ERC)
The essential functions of the conserved Smc5/6 complex remain elusive. To uncover its roles in genome maintenance, we established Saccharomyces cerevisiae cell-cycle-regulated alleles that enable restriction of Smc5/6 components to S or G2/M. Unexpectedly, the essential functions of Smc5/6 segregated fully and selectively to G2/M. Genetic screens that became possible with generated alleles identified processes that crucially rely on Smc5/6 specifically in G2/M: metabolism of DNA recombination structures triggered by endogenous replication stress, and replication through natural pausing sites located in late-replicating regions. In the first process, Smc5/6 modulates remodeling of recombination intermediates, cooperating with dissolution activities. In the second, Smc5/6 prevents chromosome fragility and toxic recombination instigated by prolonged pausing and the fork protection complex, Tof1-Csm3. Our results thus dissect Smc5/6 essential roles and reveal that combined defects in DNA damage tolerance and pausing site-replication cause recombination-mediated DNA lesions, which we propose to drive developmental and cancer-prone disorders.
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