Cnd2 has dual roles in mitotic condensation and interphase

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.

A Survey of Essential Gene Function in the Yeast Cell Division Cycle

“…Thus, our data indicate that Smc4p depletion affected the binding of Mcm2p to the regions flanking ARS1 during S phase and suggest a role for Smc4p in regulating DNA replication, perhaps in the transition from initiation to elongation. Previous work has hinted at a role for condensin in S phase, including the hydroxyurea sensitivity of condensin mutants in fission yeast (Aono et al, 2002) and the presence of condensin at the rDNA locus during S phase (Johzuka et al, 2006). Additionally, genome-wide protein-DNA interaction data suggests that Smc4p is excluded from replication origins (Wang et al, 2005), although this analysis was not performed during synchronous progression through S phase and therefore may not have detected the relevant localization.…”

MTB, the murine homolog of condensin II subunit CAP-G2, represses transcription and promotes erythroid cell differentiation

“…[1][2][3] Recent studies have provided evidence that condensin complexes and individual condensin subunits contribute to nonmitotic processes such as X-chromosome dosage compensation in Caenorhabditis elegans 4,5 epigenetic control of homeotic gene expression in Drosophila 6 and DNA repair in Saccharomyces pombe. 7 In addition to mitosis, chromosome condensation is also a common phenomenon during terminal differentiation of many hematopoietic cells, including erythroid cells, megakaryocytes and lymphocytes. As these cells become progressively more mature, nuclear chromatin becomes increasingly condensed and transcription in general is gradually repressed.…”

Nse1, Nse2, and a Novel Subunit of the Smc5-Smc6 Complex, Nse3, Play a Crucial Role in Meiosis

“…The hinge allows SMC proteins to fold back on themselves, forming an intramolecular coiled-coil and creating an ATPase by juxtaposing the Walker A and B domains (Haering et al, 2002). SMC proteins form stable heterodimers, most likely through interactions mediated by their hinge regions (Haering et al, 2002).Hypomorphic mutations of proteins in the SMC complexes render cells hypersensitive to genotoxic stress (Birkenbihl and Subramani, 1992;Lehmann et al, 1995;Sjogren and Nasmyth, 2001;Aono et al, 2002;Fujioka et al, 2002;Kim et al, 2002b;Yazdi et al, 2002;McDonald et al, 2003;Harvey et al, 2004). Cohesin may facilitate the homologous recombination repair of DSBs by holding sister-chromatids in proximity, promoting identification of an intact homologous duplex.…”