Distinct functions of condensin I and II in mitotic chromosome assembly. J Cell Sci

Research Institute of Molecular Pathology, Dr Bohr-Gasse 7, 1030 Vienna, Austria.
Journal of Cell Science (Impact Factor: 5.43). 01/2005; 117(Pt 26):6435-45. DOI: 10.1242/jcs.01604
Source: PubMed

ABSTRACT Condensin is a protein complex associated with mitotic chromosomes that has been implicated in chromosome condensation. In vertebrates, two types of condensin complexes have recently been identified, called condensin I and II. Here, we show that in mammalian cells condensin II associates with chromatin in prophase, in contrast to condensin I which is cytoplasmic and can thus interact with chromosomes only after nuclear envelope breakdown. RNA interference experiments in conjunction with imaging of live and fixed cells revealed that condensin II is required for chromosome condensation in early prophase, whereas condensin I appears to be dispensable at this stage. By contrast, condensin I is required for the complete dissociation of cohesin from chromosome arms, for chromosome shortening and for normal timing of progression through prometaphase and metaphase, whereas normal condensin II levels are dispensable for these processes. After depletion of both condensin complexes, the onset of chromosome condensation is delayed until the end of prophase, but is then initiated rapidly before nuclear envelope breakdown. These results reveal that condensin II and I associate with chromosomes sequentially and have distinct functions in mitotic chromosome assembly.

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    • "Most organisms contain two condensin complexes , condensin I and II, which share the same SMC units (MIX-1/SMC2 and SMC-4 in the worm) but differ in their regulatory subunits, termed CAPG-1, DPY-26, and DPY-28 for C. elegans condensin I and CAPG-2, KLE-2, and HCP-6 for C. elegans condensin II (Csankovszki et al., 2009; Hirano, 2012; Piazza et al., 2013; Thadani et al., 2012). In vertebrates, condensin I is cytoplasmic during interphase and appears to stabilize chromosome rigidity after nuclear envelope breakdown (Hirota et al., 2004; Ono et al., 2004). Condensin II is nuclear, is required for sister chromatid resolution during S phase, and promotes chromosomal axis formation during prophase (Cuvier and Hirano, 2003; Ono et al., 2013). "
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    ABSTRACT: During cell division, chromatin alternates between a condensed state to facilitate chromosome segregation and a decondensed form when DNA replicates. In most tissues, S phase and mitosis are separated by defined G1 and G2 gap phases, but early embryogenesis involves rapid oscillations between replication and mitosis. Using Caenorhabditis elegans embryos as a model system, we show that chromosome condensation and condensin II concentration on chromosomal axes require replicated DNA. In addition, we found that, during late telophase, replication initiates on condensed chromosomes and promotes the rapid decondensation of the chromatin. Upon replication initiation, the CDC-45-MCM-GINS (CMG) DNA helicase drives the release of condensin I complexes from chromatin and the activation or displacement of inactive MCM-2-7 complexes, which together with the nucleoporin MEL-28/ELYS tethers condensed chromatin to the nuclear envelope, thereby promoting chromatin decondensation. Our results show how, in an early embryo, the chromosome-condensation cycle is functionally linked with DNA replication. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
    Cell Reports 07/2015; 12(3). DOI:10.1016/j.celrep.2015.06.046 · 8.36 Impact Factor
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    • "Over the past two decades, accumulating lines of evidence have indicated that the chromosomal condensin complex is a principal mediator of chromosome condensation. Condensin promotes interactions between its chromosomal binding sites (Haeusler et al., 2008), its depletion or genetic mutation in organisms from yeast to vertebrates leads to defective chromosome condensation, reduced mechanical chromosome stability, and consequent chromosome segregation errors (Hirano and Mitchison, 1994; Saka et al., 1994; Strunnikov et al., 1995; Hagstrom et al., 2002; Hudson et al., 2003; Hirota et al., 2004; Oliveira et al., 2005; Thadani et al., 2012). Condensin is a member of the structural maintenance of chromosomes (SMC) family of large ringshaped multisubunit protein complexes. "
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    ABSTRACT: Mitotic chromosomes were one of the first cell biological structures to be described, yet their molecular architecture remains poorly understood. We have devised a simple biophysical model of a 300 kb-long nucleosome chain, the size of a budding yeast chromosome, constrained by interactions between binding sites of the chromosomal condensin complex, a key component of interphase and mitotic chromosomes. Comparisons of computational and experimental (4C) interaction maps, and other biophysical features, allow us to predict a mode of condensin action. Stochastic condensin-mediated pairwise interactions along the nucleosome chain generate native-like chromosome features and recapitulate chromosome compaction and individualization during mitotic condensation. Higher order interactions between condensin binding sites explain the data less well. Our results suggest that basic assumptions about chromatin behavior go a long way to explain chromosome architecture and are able to generate a molecular model of what the inside of a chromosome is likely to look like. DOI:
    eLife Sciences 04/2015; 4(4). DOI:10.7554/eLife.05565 · 9.32 Impact Factor
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    • "Molecular mechanisms of chromosome condensation in cells remain poorly understood. This is partly because only a limited number of factors have been identified, and observed condensation defects are generally mild when factors are disrupted in mitotic cells (Hirota et al., 2004; Ribeiro et al., 2009; Carpenter and Porter, 2004; Sakaguchi and Kikuchi, 2004). We rationalised that the use of Drosophila oocytes might provide a unique insight into chromosome condensation. "
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    ABSTRACT: Chromosome condensation during cell division is one of the most dramatic events in the cell cycle. Condensin and topoisomerase II are the most studied factors in chromosome condensation. However, their inactivation leads to only mild defects and little is known about roles of other factors. Here we took advantage of Drosophila oocytes to elucidate the roles of potential condensation factors by RNAi. Consistent with previous studies, depletion of condensin I subunits or topoisomerase II in oocytes only mildly affected chromosome condensation. In contrast, we found severe undercondensation of chromosomes after depletion of the Mi-2 containing NuRD nucleosome remodelling complex or the protein kinase NHK-1. The further phenotypic analysis suggests that Mi-2 and NHK-1 are involved in different pathways in chromosome condensation. We show that the main role of NHK-1 in chromosome condensation is to phosphorylate BAF and suppress its activity in linking chromosomes to nuclear envelope proteins. We further showed that NHK-1 is important for chromosome condensation in mitosis as well as in oocytes.
    Development 12/2014; 142(4). DOI:10.1242/jcs.158477 · 6.46 Impact Factor
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