Cyclin A2 is required for sister chromatid segregation, but not separase control, in mouse oocyte meiosis

Cell Rep. 2012 Nov 29;2(5):1077-87. doi: 10.1016/j.celrep.2012.10.002. Epub 2012 Nov 1.

Abstract

In meiosis, two specialized cell divisions allow the separation of paired chromosomes first, then of sister chromatids. Separase removes the cohesin complex holding sister chromatids together in a stepwise manner from chromosome arms in meiosis I, then from the centromere region in meiosis II. Using mouse oocytes, our study reveals that cyclin A2 promotes entry into meiosis, as well as an additional unexpected role; namely, its requirement for separase-dependent sister chromatid separation in meiosis II. Untimely cyclin A2-associated kinase activity in meiosis I leads to precocious sister separation, whereas inhibition of cyclin A2 in meiosis II prevents it. Accordingly, endogenous cyclin A is localized to kinetochores throughout meiosis II, but not in anaphase I. Additionally, we found that cyclin B1, but not cyclin A2, inhibits separase in meiosis I. These findings indicate that separase-dependent cohesin removal is differentially regulated by cyclin B1 and A2 in mammalian meiosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaphase
  • Animals
  • Carrier Proteins / metabolism
  • Cell Cycle Proteins / antagonists & inhibitors
  • Cell Cycle Proteins / metabolism*
  • Cells, Cultured
  • Centromere / metabolism
  • Chromatids / metabolism*
  • Chromosome Segregation
  • Cyclin A2 / antagonists & inhibitors
  • Cyclin A2 / genetics
  • Cyclin A2 / metabolism*
  • Cyclin B1 / metabolism
  • Cyclin-Dependent Kinases / antagonists & inhibitors
  • Cyclin-Dependent Kinases / metabolism
  • Endopeptidases / metabolism*
  • Kinetochores / metabolism
  • Meiosis*
  • Metaphase
  • Mice
  • Oocytes / cytology
  • Oocytes / metabolism*
  • Securin
  • Separase

Substances

  • Carrier Proteins
  • Cell Cycle Proteins
  • Cyclin A2
  • Cyclin B1
  • Securin
  • Cyclin-Dependent Kinases
  • Endopeptidases
  • Separase