Phosphorylation of the RecQ Helicase Sgs1/BLM Controls Its DNA Unwinding Activity during Meiosis and Mitosis

Dev Cell. 2020 Jun 22;53(6):706-723.e5. doi: 10.1016/j.devcel.2020.05.016. Epub 2020 Jun 5.

Abstract

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • DNA, Fungal / genetics
  • Homologous Recombination
  • Meiosis*
  • Mitosis*
  • Phosphorylation
  • Protein Processing, Post-Translational*
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • RecQ Helicases / genetics
  • RecQ Helicases / metabolism*
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • Cell Cycle Proteins
  • DNA, Fungal
  • Saccharomyces cerevisiae Proteins
  • Protein Serine-Threonine Kinases
  • CDC5 protein, S cerevisiae
  • SGS1 protein, S cerevisiae
  • RecQ Helicases