Essential role of the Cdk2 activator RingoA in meiotic telomere tethering to the nuclear envelope

Nat Commun. 2016 Mar 30;7:11084. doi: 10.1038/ncomms11084.

Abstract

Cyclin-dependent kinases (CDKs) play key roles in cell cycle regulation. Genetic analysis in mice has revealed an essential role for Cdk2 in meiosis, which renders Cdk2 knockout (KO) mice sterile. Here we show that mice deficient in RingoA, an atypical activator of Cdk1 and Cdk2 that has no amino acid sequence homology to cyclins, are sterile and display meiotic defects virtually identical to those observed in Cdk2 KO mice including non-homologous chromosome pairing, unrepaired double-strand breaks, undetectable sex-body and pachytene arrest. Interestingly, RingoA is required for Cdk2 targeting to telomeres and RingoA KO spermatocytes display severely affected telomere tethering as well as impaired distribution of Sun1, a protein essential for the attachment of telomeres to the nuclear envelope. Our results identify RingoA as an important activator of Cdk2 at meiotic telomeres, and provide genetic evidence for a physiological function of mammalian Cdk2 that is not dependent on cyclins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle Checkpoints
  • Cell Cycle Proteins / metabolism*
  • Chromosome Pairing
  • Cyclin-Dependent Kinase 2 / metabolism*
  • DNA Breaks, Double-Stranded
  • DNA Repair
  • Humans
  • Infertility, Male / metabolism
  • Infertility, Male / pathology
  • Male
  • Meiosis*
  • Meiotic Prophase I
  • Membrane Proteins / metabolism
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microtubule-Associated Proteins / metabolism
  • Nuclear Envelope / metabolism*
  • Nuclear Proteins / metabolism
  • Pachytene Stage
  • Protein Binding
  • Spermatocytes / pathology
  • Telomere / metabolism*

Substances

  • Cell Cycle Proteins
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Nuclear Proteins
  • SUN1 protein, human
  • Spy1 protein, mouse
  • Cyclin-Dependent Kinase 2