Mad2 prevents aneuploidy and premature proteolysis of cyclin B and securin during meiosis I in mouse oocytes.
In mitosis, the spindle checkpoint protein Mad2 averts aneuploidy by delaying anaphase onset until chromosomes align. Here we show that depletion of Mad2 in meiosis I mouse oocytes induced an increased incidence of aneuploidy. Proteolysis of cyclin B and securin commenced earlier in Mad2-depleted oocytes, resulting in a shortened duration of meiosis I. Furthermore, overexpression of Mad2 inhibited homolog disjunction. We conclude that Mad2 delays the onset of cyclin B and securin degradation and averts aneuploidy during meiosis I in mammalian oocytes. The data suggest a link between trisomies such as Down syndrome and defective oocyte spindle checkpoint function.
Homer
Hayden A
HA
Newcastle Fertility Centre at Life, Centre for Life, Newcastle upon Tyne NE1 4EP, United Kingdom. h.a.homer@ncl.ac.uk
McDougall
Alex
A
Levasseur
Mark
M
Yallop
Katie
K
Murdoch
Alison P
AP
Herbert
Mary
M
D000705:Anaphase / Q000502:physiology; D000782:Aneuploidy; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins; D019926:Cyclin B / Q000378:metabolism*; D004314:Down Syndrome / Q000235:genetics / Q000378:metabolism; D064246:Mad2 Proteins; D049469:Meiotic Prophase I / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008938:Mitosis / Q000235:genetics / Q000502:physiology; D009687:Nuclear Proteins; D009865:Oocytes / Q000166:cytology / Q000502:physiology*; D064249:Securin
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D019926:Cyclin B; D064246:Mad2 Proteins; C577698:Mad2l1 protein, mouse; C577699:Mad2l2 protein, mouse; D009687:Nuclear Proteins; D064249:Securin