title: The roles of MAD1, MAD2 and MAD3 in meiotic progression and the segregation of nonexchange chromosomes.
abstract: Errors in meiotic chromosome segregation are the leading cause of spontaneous abortions and birth defects. In humans, chromosomes that fail to experience crossovers (or exchanges) are error-prone, more likely than exchange chromosomes to mis-segregate in meiosis. We used a yeast model to investigate the mechanisms that partition nonexchange chromosomes. These studies showed that the spindle checkpoint genes MAD1, MAD2 and MAD3 have different roles. We identified a new meiotic role for MAD3; though dispensable for the segregation of exchange chromosomes, it is essential for the segregation of nonexchange chromosomes. This function of Mad3p could also be carried out by human BubR1. MAD1 and MAD2 act in a surveillance mechanism that mediates a metaphase delay in response to nonexchange chromosomes, whereas MAD3 acts as a crucial meiotic timer, mediating a prophase delay in every meiosis. These findings suggest plausible models for the basis of errant meiotic segregation in humans.
authors.affiliation: Program in Genetics, Sackler School of BioMedical Sciences, Tufts University School of Medicine, 136 Harrison Avenue, Boston, Massachusetts 02111, USA.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Cheslock
authors.forename: Benedict J
authors.initials: BJ
authors.lastname: Kemp
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Boumil
authors.forename: Dean S
authors.initials: DS
authors.lastname: Dawson
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002503:Centromere / Q000235:genetics / Q000378:metabolism; D020090:Chromosome Segregation / Q000235:genetics / Q000502:physiology*; D015825:Chromosomes, Fungal / Q000235:genetics* / Q000378:metabolism; D005656:Fungal Proteins; D006801:Humans; D064246:Mad2 Proteins; D008540:Meiosis / Q000235:genetics / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011995:Recombination, Genetic / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins
chemical_list: D018797:Cell Cycle Proteins; D005656:Fungal Proteins; C501382:MAD1 protein, S cerevisiae; C501384:MAD1L1 protein, human; C577695:MAD2 protein, S cerevisiae; C406764:MAD3 protein, S cerevisiae; D064246:Mad2 Proteins; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; C584277:BUB1 protein, human; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases