Cnd2 has dual roles in mitotic condensation and interphase

Nature. 2002 May 9;417(6885):197-202. doi: 10.1038/417197a.

Abstract

Chromosome condensation requires condensin, which comprises five subunits. Two of these subunits--both being structural maintenance of chromosome (SMC) proteins-are coiled-coils with globular terminal domains that interact with ATP and DNA. The remaining three, non-SMC subunits also have essential, albeit undefined, roles in condensation. Here we report that Cnd2 (ref. 6), a non-SMC subunit of fission yeast similar to Drosophila Barren and the budding yeast protein Brn1 (refs 8, 9), is required for both interphase and mitotic condensation. In cnd2-1 mutants, ultraviolet-induced DNA damage is not repaired, and cells arrested by hydroxyurea do not recover. A definitive defect of interphase is abolishment of Cds1 (a checkpoint kinase) activation in the presence of hydroxyurea in both cnd2-1 mutant cells and in cells where other condensin subunits have been genetically disrupted. In the absence of hydroxyurea, a G2 checkpoint delay occurred in cnd2-1 mutants in a manner dependent on Cds1 and ATM-like Rad3, but not Chk1 (refs 10-13), before the mitotic condensation defect. Furthermore, cnd2-1 was synthetic-lethal with mutations of excision repair, RecQ helicase and DNA replication enzymes. These interphase and mitotic defects provide insight into the mechanistic role of non-SMC subunits that interact with the globular SMC domains in the heteropentameric holocomplex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Checkpoint Kinase 1
  • Checkpoint Kinase 2
  • Chromosomes, Fungal / chemistry
  • Chromosomes, Fungal / genetics
  • Chromosomes, Fungal / metabolism*
  • DNA Damage / radiation effects
  • DNA Repair
  • G2 Phase / drug effects
  • G2 Phase / radiation effects
  • Genes, Fungal / genetics
  • Hydroxyurea / pharmacology
  • Interphase* / drug effects
  • Interphase* / radiation effects
  • Mitosis* / drug effects
  • Mitosis* / radiation effects
  • Molecular Conformation
  • Mutation / genetics
  • Protein Kinases / genetics
  • Protein Structure, Tertiary
  • Protein Subunits
  • Protein-Serine-Threonine Kinases*
  • Schizosaccharomyces / cytology*
  • Schizosaccharomyces / drug effects
  • Schizosaccharomyces / genetics
  • Schizosaccharomyces / metabolism*
  • Schizosaccharomyces pombe Proteins / chemistry
  • Schizosaccharomyces pombe Proteins / genetics
  • Schizosaccharomyces pombe Proteins / metabolism*
  • Temperature
  • Ultraviolet Rays

Substances

  • Cell Cycle Proteins
  • Cnd2 protein, S pombe
  • Protein Subunits
  • Schizosaccharomyces pombe Proteins
  • Protein Kinases
  • Checkpoint Kinase 2
  • Cds1 protein, S pombe
  • Checkpoint Kinase 1
  • Chk1 protein, S pombe
  • Protein-Serine-Threonine Kinases
  • Hydroxyurea