Regulation of meiotic recombination via Mek1-mediated Rad54 phosphorylation

Hengyao Niu1, Lihong Wan, Valeria Busygina

  • 1Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794-5215, USA.

Molecular Cell
|November 18, 2009
PubMed

Insights

Meiosis uses Mek1 kinase to control DNA recombination by inhibiting Rad51 recombinase activity. This ensures homologs are preferred over sister chromatids, preventing errors during cell division.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • Homologous recombination (HR) differs between meiosis and mitosis.
  • Meiosis favors interhomolog recombination, while mitosis favors sister chromatid engagement.
  • In budding yeast, Dmc1 and Mek1 are crucial for meiotic interhomolog bias, with Mek1 suppressing Rad51 on sister chromatids.

Purpose of the Study:

  • To investigate the additional roles of Mek1 in controlling recombination partner choice during meiosis.
  • To elucidate the mechanism by which Mek1 regulates the activity of the Rad51 recombinase.

Main Methods:

  • Proteomic analysis
  • Biochemical assays
  • Genetic approaches

Main Results:

  • Mek1 inhibits Rad51 activity by phosphorylating its partner, Rad54, at threonine 132.
  • Phosphorylation at threonine 132 attenuates Rad51/Rad54 complex formation.
  • This phosphorylation reduces Rad51 function both in vitro and in vivo.
  • Mek1 also suppresses sister chromatid invasion independently of Rad54.

Conclusions:

  • Mek1 phosphorylation of Rad54 is a key mechanism controlling recombination partner choice in meiosis.
  • This regulation ensures accurate chromosome segregation by favoring homologs over sister chromatids.
  • Mek1 employs dual mechanisms, involving Rad54 and a Rad54-independent pathway, to control Rad51 activity.

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