Spindle assembly checkpoint of oocytes depends on a kinetochore structure determined by cohesin in meiosis I

Curr Biol. 2013 Dec 16;23(24):2534-9. doi: 10.1016/j.cub.2013.10.052. Epub 2013 Nov 27.

Abstract

Since the dissolution of sister chromatid cohesion by separase and cyclin B destruction is irreversible, it is essential to delay both until all chromosomes have bioriented on the mitotic spindle. Kinetochores that are not correctly attached to the spindle generate the mitotic checkpoint complex (MCC), which inhibits the anaphase-promoting complex/cyclosome (APC/C) and blocks anaphase onset. This process is known as the spindle assembly checkpoint (SAC). The SAC is especially important in meiosis I, where bivalents consisting of homologous chromosomes held together by chiasmata biorient. Since the first meiotic division is unaffected by rare achiasmatic chromosomes or misaligned bivalents, it is thought that several tensionless kinetochores are required to produce sufficient MCC for APC/C inhibition. Consistent with this, univalents lacking chiasmata elicit a SAC-mediated arrest in Mlh1(-/-) oocytes. In contrast, chromatids generated by TEV protease-induced cohesin cleavage in Rec8(TEV/TEV) oocytes merely delay APC/C activation. Since the arrest of Mlh1(-/-)Rec8(TEV/TEV) oocytes is alleviated by TEV protease, even when targeted to kinetochores, we conclude that their SAC depends on cohesin as well as dedicated kinetochore proteins. This has important implications for aging oocytes, where cohesin deterioration will induce sister kinetochore biorientation and compromise MCC production, leading to chromosome missegregation and aneuploid fetuses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle Proteins / metabolism
  • Cell Cycle Proteins / physiology*
  • Chromatids / metabolism
  • Chromosomal Proteins, Non-Histone / metabolism
  • Chromosomal Proteins, Non-Histone / physiology*
  • Female
  • Kinetochores / physiology
  • Kinetochores / ultrastructure*
  • M Phase Cell Cycle Checkpoints*
  • Meiosis*
  • Mice
  • Oocytes / cytology*
  • Time-Lapse Imaging

Substances

  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • cohesins