Mnd2, an essential antagonist of the anaphase-promoting complex during meiotic prophase.
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.
Penkner
Alexandra M
AM
Vienna Biocenter II, Max Perutz Laboratories, Department of Chromosome Biology, Vienna, Austria.
Prinz
Susanne
S
Ferscha
Stefan
S
Klein
Franz
F
D064173:Anaphase-Promoting Complex-Cyclosome; D064199:Cdc20 Proteins; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002842:Chromatids / Q000235:genetics / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone; D020090:Chromosome Segregation / Q000235:genetics / Q000502:physiology*; D010450:Endopeptidases; D005656:Fungal Proteins; D018093:Gelatinases / Q000235:genetics / Q000378:metabolism; D008540:Meiosis / Q000235:genetics / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011489:Protein Denaturation; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D064249:Securin; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D043743:Ubiquitin-Protein Ligase Complexes / Q000235:genetics / Q000378:metabolism*; D000097722:Cohesins; D000099167:Fibroblast Activation Protein Alpha
D064173:Anaphase-Promoting Complex-Cyclosome; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D010450:Endopeptidases; D005656:Fungal Proteins; D018093:Gelatinases; D008565:Membrane Proteins; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D064249:Securin; D012697:Serine Endopeptidases; D043743:Ubiquitin-Protein Ligase Complexes; D000097722:Cohesins; D000099167:Fibroblast Activation Protein Alpha; C577515:Ama1 protein, S cerevisiae; C577495:CDC20 protein, S cerevisiae; C577468:MND2 protein, S cerevisiae; C578004:PDS1 protein, S cerevisiae; C482640:Sgo1 protein, S cerevisiae