title: The yeast CDC37 gene interacts with MPS1 and is required for proper execution of spindle pole body duplication.
abstract: The MPS1 gene from Saccharomyces cerevisiae encodes an essential protein kinase required for spindle pole body (SPB) duplication and for the mitotic spindle assembly checkpoint. Cells with the mps1-1 mutation fail early in SPB duplication and proceed through monopolar mitosis with lethal consequences. We identified CDC37 as a multicopy suppressor of mps1-1 temperature-sensitive growth. Suppression is allele specific, and synthetic lethal interactions occur between mps1 and cdc37 alleles. We examined the cdc37-1 phenotype for defects related to the SPB cycle. The cdc37-1 temperature-sensitive allele causes unbudded, G1 arrest at Start (Reed, S.I. 1980. Genetics. 95: 561-577). Reciprocal shifts demonstrate that cdc37-1 arrest is interdependent with alpha-factor arrest but is not a normal Start arrest. Although the cells are responsive to alpha-factor at the arrest, SPB duplication is uncoupled from other aspects of G1 progression and proceeds past the satellite-bearing SPB stage normally seen at Start. Electron microscopy reveals side-by-side SPBs at cdc37-1 arrest. The outer plaque of one SPB is missing or reduced, while the other is normal. Using the mps2-1 mutation to distinguish between the SPBs, we find that the outer plaque defect is specific to the new SPB. This phenotype may arise in part from reduced Mps1p function: although Mps1p protein levels are unaffected by the cdc37-1 mutation, kinase activity is markedly reduced. These data demonstrate a requirement for CDC37 in SPB duplication and suggest a role for this gene in G1 control. CDC37 may provide a chaperone function that promotes the activity of protein kinases.
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Colorado-Boulder, 80309-0347, USA.
authors.forename: A R
authors.initials: AR
authors.lastname: Schutz
authors.forename: T H
authors.initials: TH
authors.lastname: Giddings
authors.forename: E
authors.initials: E
authors.lastname: Steiner
authors.forename: M
authors.initials: M
authors.lastname: Winey
mesh_terms: D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D029721:Drosophila Proteins; D004843:Epistasis, Genetic; D005800:Genes, Fungal / Q000502:physiology; D016153:Genes, Suppressor / Q000502:physiology; D008938:Mitosis; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011993:Recombinant Fusion Proteins; D015183:Restriction Mapping; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics* / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins; D008941:Spindle Apparatus / Q000378:metabolism*
chemical_list: C513270:CDC37 protein, S cerevisiae; D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D018832:Molecular Chaperones; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; C093416:MPS1 protein, S cerevisiae