How cells regulate DNA repair during meiosis and mitosis
Grigaitis et al. show that the Bloom’s helicase ortholog, Sgs1, is sequentially phosphorylated by two cell cycle kinases: CDK and Cdc5/PLK. Phosphorylation regulates DNA unwinding by Sgs1, which is required for efficient mitotic and meiotic DNA repair. Context-specific changes in Sgs1 helicase activity influence recombination outcome (noncrossover vs. crossover).
RecQ helicases are conserved in all domains of life and human germline mutations in three family members – BLM, WRN and RECQL4 – give rise to debilitating disorders, including a strong predisposition to cancers, premature ageing and reduced fertility. Work spanning the last four decades uncovered a multitude of RecQ helicase functions, including roles in DNA replication, transcription, DNA damage signaling and DNA repair. One hallmark feature of all such functions is that they are highly prevalent during S-phase. In this work, we obtained experimental evidence demonstrating that the Bloom’s helicase ortholog Sgs1 is regulated in both meiotic and mitotically dividing yeast cells. Notably, cell cycle regulated phosphorylation stimulates Sgs1 function during S-phase/prophase I, which is required for efficient DNA repair. We speculate that the regulatory mechanism uncovered here might constitute just a first example of how RecQ helicases are wired to S-phase progression, ensuring stable propagation of the newly replicated genome.
Link to the paper in external page Developmental Cell.