The yeast APC/C subunit Mnd2 prevents premature sister chromatid separation triggered by the meiosis-specific APC/C-Ama1.
Cohesion established between sister chromatids during pre-meiotic DNA replication mediates two rounds of chromosome segregation. The first division is preceded by an extended prophase wherein homologous chromosomes undergo recombination. The persistence of cohesion during prophase is essential for recombination and both meiotic divisions. Here we show that Mnd2, a subunit of the anaphase-promoting complex (APC/C) from budding yeast, is essential to prevent premature destruction of cohesion in meiosis. During S- and prophase, Mnd2 prevents activation of the APC/C by a meiosis-specific activator called Ama1. In cells lacking Mnd2 the APC/C-Ama1 enzyme triggers degradation of Pds1, which causes premature sister chromatid separation due to unrestrained separase activity. In vitro, Mnd2 inhibits ubiquitination of Pds1 by APC/C-Ama1 but not by other APC/C holo-enzymes. We conclude that chromosome segregation in meiosis depends on the selective inhibition of a meiosis-specific form of the APC/C.
Oelschlaegel
Tobias
T
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
Schwickart
Martin
M
Matos
Joao
J
Bogdanova
Aliona
A
Camasses
Alain
A
Havlis
Jan
J
Shevchenko
Andrej
A
Zachariae
Wolfgang
W
D000705:Anaphase / Q000235:genetics / Q000502:physiology; D064173:Anaphase-Promoting Complex-Cyclosome; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism; D017489:CDC28 Protein Kinase, S cerevisiae / Q000235:genetics / Q000378:metabolism; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002842:Chromatids / Q000235:genetics / Q000378:metabolism; D020090:Chromosome Segregation / Q000235:genetics / Q000502:physiology*; D010450:Endopeptidases / Q000378:metabolism; D008540:Meiosis / Q000235:genetics / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011489:Protein Denaturation / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D064249:Securin; D064247:Separase; D043743:Ubiquitin-Protein Ligase Complexes / Q000235:genetics / Q000378:metabolism*
C577515:Ama1 protein, S cerevisiae; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins; C577468:MND2 protein, S cerevisiae; D009687:Nuclear Proteins; C578004:PDS1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D064249:Securin; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D016203:CDC2 Protein Kinase; D017489:CDC28 Protein Kinase, S cerevisiae; D010450:Endopeptidases; C577986:ESP1 protein, S cerevisiae; D064247:Separase