Apc10 and Ste9/Srw1, two regulators of the APC-cyclosome, as well as the CDK inhibitor Rum1 are required for G1 cell-cycle arrest in fission yeast

EMBO J. 1998 Sep 15;17(18):5388-99. doi: 10.1093/emboj/17.18.5388.

Abstract

Many eukaryotic cells arrest the cell cycle at G1 phase upon nutrient deprivation. In fission yeast, during nitrogen starvation, cells divide twice and arrest at G1. We have isolated a novel type of sterile mutant, which undergoes one additional S phase upon starvation and, as a result, arrests at G2. Three loci (apc10, ste9/srw1 and rum1) were identified. The apc10 mutants, previously unidentified, show, in addition to sterility, temperature-sensitive growth with defects in chromosome segregation. apc10(+) is essential for viability, encodes a conserved protein (a homologue of budding yeast Apc10/Doc1) and is required for ubiquitination and degradation of mitotic B-type cyclins. Apc10 does not co-sediment with the 20S APC-cyclosome, a ubiquitin ligase for B-type cyclins, and in the apc10 mutant the 20S complex is intact, suggesting that it is a novel regulator for this complex. A subpopulation of Apc10 does co-immunoprecipitate with the anaphase-promoting complex (APC). A second gene, ste9(+)/srw1(+), encodes a member of the fizzy-related family, also regulators of the APC. Finally, Rum1 is a cyclin-dependent kinase (CDK) inhibitor which exists only in G1. The results suggest that dual downregulation of CDK, one via the APC and the other via the CDK inhibitor, is a universal mechanism that is used to arrest cell cycle progression at G1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Anaphase-Promoting Complex-Cyclosome
  • Base Sequence
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Cloning, Molecular
  • Cyclin B
  • Cyclin-Dependent Kinases / antagonists & inhibitors
  • Cyclins / genetics
  • Cyclins / physiology
  • Enzyme Inhibitors
  • Fungal Proteins / genetics*
  • G1 Phase / genetics*
  • Genes, Essential / physiology
  • Genes, Fungal / physiology
  • Genetic Complementation Test
  • Ligases / metabolism*
  • Molecular Sequence Data
  • Mutation / physiology
  • S Phase
  • Schizosaccharomyces / genetics*
  • Schizosaccharomyces pombe Proteins*
  • Sequence Homology, Amino Acid
  • Ubiquitin-Protein Ligase Complexes*
  • Ubiquitin-Protein Ligases
  • Ubiquitins / metabolism

Substances

  • Cell Cycle Proteins
  • Cig2 protein, S pombe
  • Cyclin B
  • Cyclins
  • Enzyme Inhibitors
  • Fungal Proteins
  • Rum1 protein, S pombe
  • Schizosaccharomyces pombe Proteins
  • Ubiquitins
  • cdc18 protein, S pombe
  • srw1 protein, S pombe
  • Ubiquitin-Protein Ligase Complexes
  • Anaphase-Promoting Complex-Cyclosome
  • Ubiquitin-Protein Ligases
  • Cyclin-Dependent Kinases
  • Ligases

Associated data

  • GENBANK/AB012919