The Bloom’s helicase ortholog, Sgs1, orchestrates the formation and disengagement of recombination intermediates to enable controlled crossing-over during meiotic and mitotic DNA repair. Whether its enzymatic activity is temporally regulated to implement formation of noncrossovers prior to the activation of crossover-nucleases is unknown. Here, we show that, akin to the Mus81-Mms4, Yen1, and MutLγ-Exo1 nucleases, Sgs1 helicase function is under cell-cycle control through the actions of CDK and Cdc5 kinases. Notably, however, whereas CDK and Cdc5 unleash nuclease function during M phase, they act in concert to stimulate Sgs1 activity during S phase/prophase I. Mechanistically, CDK-mediated phosphorylation enhances the velocity and processivity of Sgs1, which stimulates DNA unwinding in vitro and joint molecule processing in vivo. Subsequent hyper-phosphorylation by Cdc5 appears to reduce the activity of Sgs1, while activating Mus81-Mms4 and MutLγ-Exo1. These findings suggest a concerted mechanism driving orderly formation of noncrossover and crossover recombinants in meiotic and mitotic cells.

Bloom的解旋酶直向同源物Sgs1负责重组中间产物的形成和分离，以在减数分裂和有丝分裂DNA修复过程中实现受控的交换。在激活交叉核酸酶之前，是否暂时调节其酶活性以实现非交叉的形成尚不清楚。在这里，我们表明，类似于Mus81-Mms4，Yen1和MutLγ-Exo1核酸酶，Sgs1解旋酶的功能受CDK和Cdc5激酶作用的细胞周期控制。值得注意的是，然而，然而CDK和Cdc5期间M期释放核酸酶的功能，它们共同作用在S期，刺激SGS1活性/前期I.机械地，CDK介导的磷酸化增强SGS1的速度和持续合成能力，其刺激DNA开卷体外和体内关节分子加工。随后的Cdc5的过度磷酸化似乎会降低Sgs1的活性，同时激活Mus81-Mms4和MutLγ-Exo1。这些发现表明在减数分裂和有丝分裂细胞中驱动非交叉和交叉重组子的有序形成的协调机制。