Developmental Cell
Volume 53, Issue 6, 22 June 2020, Pages 706-723.e5
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Article
Phosphorylation of the RecQ Helicase Sgs1/BLM Controls Its DNA Unwinding Activity during Meiosis and Mitosis

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Highlights

  • S-CDK and Cdc5 kinases sequentially phosphorylate Sgs1 during the cell cycle

  • CDK phosphorylation enhances the DNA unwinding activity of Sgs1

  • Phosphorylation increases the velocity and processivity of Sgs1 molecules

  • Phospho-stimulation of Sgs1 is required for mitotic and meiotic DNA repair

Summary

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.

Keywords

DNA repair
meiosis
mitosis
cell cycle
noncrossover
crossover
Sgs1(BLM)-Top3-Rmi1
Cdc28(CDK1)
Cdc5(PLK1)
homologous recombination

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These authors contributed equally

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