Mnd2, an essential antagonist of the anaphase-promoting complex during meiotic prophase

Cell. 2005 Mar 25;120(6):789-801. doi: 10.1016/j.cell.2005.01.017.

Abstract

Meiotic cohesin serves in sister chromatid linkage and DNA repair until its subunit Rec8 is cleaved by separase. Separase is activated when its inhibitor, securin, is polyubiquitinated by the Cdc20 regulated anaphase-promoting complex (APC(Cdc20)) and consequently degraded. Differently regulated APCs (APC(Cdh1), APC(Ama1)) have not been implicated in securin degradation at meiosis I. We show that Mnd2, a factor known to associate with APC components, prevents premature securin degradation in meiosis by APC(Ama1). mnd2Delta cells lack linear chromosome axes and exhibit precocious sister chromatid separation, but deletion of AMA1 suppresses these defects. Besides securin, Sgo1, a protein essential for protection of centromeric cohesion during anaphase I, is also destabilized in mnd2delta cells. Mnd2's disappearance prior to anaphase II may activate APC(Ama1). Human oocytes may spend many years in meiotic prophase before maturation. Inhibitors of meiotic APC variants could prevent loss of chiasmata also in these cells, thereby guarding against aberrant chromosome segregation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaphase-Promoting Complex-Cyclosome
  • Cdc20 Proteins
  • Cell Cycle / genetics
  • Cell Cycle / physiology*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Chromatids / genetics
  • Chromatids / metabolism
  • Chromosomal Proteins, Non-Histone
  • Chromosome Segregation / genetics
  • Chromosome Segregation / physiology*
  • Fungal Proteins
  • Gelatinases / genetics
  • Gelatinases / metabolism
  • Meiosis / genetics
  • Meiosis / physiology*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mutation / genetics
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Protein Denaturation
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Securin
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / metabolism
  • Ubiquitin-Protein Ligase Complexes / genetics
  • Ubiquitin-Protein Ligase Complexes / metabolism*

Substances

  • Ama1 protein, S cerevisiae
  • CDC20 protein, S cerevisiae
  • Cdc20 Proteins
  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • Fungal Proteins
  • MND2 protein, S cerevisiae
  • Membrane Proteins
  • Nuclear Proteins
  • PDS1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Securin
  • Sgo1 protein, S cerevisiae
  • cohesins
  • Ubiquitin-Protein Ligase Complexes
  • Anaphase-Promoting Complex-Cyclosome
  • Serine Endopeptidases
  • fibroblast activation protein alpha
  • Gelatinases