Cnd2 has dual roles in mitotic condensation and interphase.
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.
Aono
Nobuki
N
Graduate School of Biostatistics, Department of Gene Mechanisms, Kyoto University, Japan.
Sutani
Takashi
T
Tomonaga
Takeshi
T
Mochida
Satoru
S
Yanagida
Mitsuhiro
M
D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000071877:Checkpoint Kinase 1; D064447:Checkpoint Kinase 2; D015825:Chromosomes, Fungal / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage / Q000528:radiation effects; D004260:DNA Repair; D016195:G2 Phase / Q000187:drug effects / Q000528:radiation effects; D005800:Genes, Fungal / Q000235:genetics; D006918:Hydroxyurea / Q000494:pharmacology; D007399:Interphase / Q000187:drug effects / Q000528:radiation effects; D008938:Mitosis / Q000187:drug effects / Q000528:radiation effects; D008968:Molecular Conformation; D009154:Mutation / Q000235:genetics; D011494:Protein Kinases / Q000235:genetics; D017346:Protein Serine-Threonine Kinases; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D012568:Schizosaccharomyces / Q000166:cytology* / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013696:Temperature; D014466:Ultraviolet Rays
D018797:Cell Cycle Proteins; C454839:Cnd2 protein, S pombe; D021122:Protein Subunits; D029702:Schizosaccharomyces pombe Proteins; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C578636:Cds1 protein, S pombe; D000071877:Checkpoint Kinase 1; C000605873:Chk1 protein, S pombe; D017346:Protein Serine-Threonine Kinases; D006918:Hydroxyurea