title: The spindle checkpoint protein Mad2 regulates APC/C activity during prometaphase and metaphase of meiosis I in Saccharomyces cerevisiae.
abstract: In many eukaryotes, disruption of the spindle checkpoint protein Mad2 results in an increase in meiosis I nondisjunction, suggesting that Mad2 has a conserved role in ensuring faithful chromosome segregation in meiosis. To characterize the meiotic function of Mad2, we analyzed individual budding yeast cells undergoing meiosis. We find that Mad2 sets the duration of meiosis I by regulating the activity of APC(Cdc20). In the absence of Mad2, most cells undergo both meiotic divisions, but securin, a substrate of the APC/C, is degraded prematurely, and prometaphase I/metaphase I is accelerated. Some mad2Δ cells have a misregulation of meiotic cell cycle events and undergo a single aberrant division in which sister chromatids separate. In these cells, both APC(Cdc20) and APC(Ama1) are prematurely active, and meiosis I and meiosis II events occur in a single meiotic division. We show that Mad2 indirectly regulates APC(Ama1) activity by decreasing APC(Cdc20) activity. We propose that Mad2 is an important meiotic cell cycle regulator that ensures the timely degradation of APC/C substrates and the proper orchestration of the meiotic divisions.
authors.affiliation: Department of Biology, Indiana University, Bloomington, IN 47405, USA.
authors.forename: Dai
authors.initials: D
authors.lastname: Tsuchiya
authors.forename: Claire
authors.initials: C
authors.lastname: Gonzalez
authors.forename: Soni
authors.initials: S
authors.lastname: Lacefield
mesh_terms: D064173:Anaphase-Promoting Complex-Cyclosome; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002466:Cell Nucleolus / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D055786:Gene Knockout Techniques; D018386:Kinetochores / Q000378:metabolism; D059566:M Phase Cell Cycle Checkpoints; D064246:Mad2 Proteins; D008540:Meiosis; D008677:Metaphase; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D049468:Prometaphase; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013170:Spores / Q000378:metabolism; D059008:Time-Lapse Imaging; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism*
chemical_list: C577515:Ama1 protein, S cerevisiae; C074860:CDC14 protein, S cerevisiae; C577495:CDC20 protein, S cerevisiae; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; C577695:MAD2 protein, S cerevisiae; D064246:Mad2 Proteins; D009687:Nuclear Proteins; C502898:REC8 protein, S cerevisiae; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D017027:Protein Tyrosine Phosphatases