title: C. elegans condensin promotes mitotic chromosome architecture, centromere organization, and sister chromatid segregation during mitosis and meiosis.
abstract: Chromosome segregation and X-chromosome gene regulation in Caenorhabditis elegans share the component MIX-1, a mitotic protein that also represses X-linked genes during dosage compensation. MIX-1 achieves its dual roles through interactions with different protein partners. To repress gene expression, MIX-1 acts in an X-chromosome complex that resembles the mitotic condensin complex yet lacks chromosome segregation function. Here we show that MIX-1 interacts with a mitotic condensin subunit, SMC-4, to achieve chromosome segregation. The SMC-4/MIX-1 complex positively supercoils DNA in vitro and is required for mitotic chromosome structure and segregation in vivo. Thus, C. elegans has two condensin complexes, one conserved for mitosis and another specialized for gene regulation. SMC-4 and MIX-1 colocalize with centromere proteins on condensed mitotic chromosomes and are required for the restricted orientation of centromeres toward spindle poles. This cell cycle-dependent localization requires AIR-2/AuroraB kinase. Depletion of SMC-4/MIX-1 causes aberrant mitotic chromosome structure and segregation, but not dramatic decondensation at metaphase. Moreover, SMC-4/MIX-1 depletion disrupts sister chromatid segregation during meiosis II but not homologous chromosome segregation during meiosis I, although both processes require chromosome condensation. These results imply that condensin is not simply required for compaction, but plays a more complex role in chromosome architecture that is essential for mitotic and meiotic sister chromatid segregation.
authors.affiliation: Howard Hughes Medical Institute, University of California, Berkeley, CA 94720-3204, USA.
authors.forename: Kirsten A
authors.initials: KA
authors.lastname: Hagstrom
authors.forename: Victor F
authors.initials: VF
authors.lastname: Holmes
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Cozzarelli
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Meyer
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D064096:Aurora Kinase A; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017173:Caenorhabditis elegans / Q000737:chemistry / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism; D002503:Centromere / Q000737:chemistry / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D004278:DNA, Superhelical; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D004303:Dosage Compensation, Genetic; D008040:Genetic Linkage; D015801:Helminth Proteins / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D017404:In Situ Hybridization, Fluorescence; D008540:Meiosis; D008856:Microscopy, Fluorescence; D008938:Mitosis; D046912:Multiprotein Complexes; D010766:Phosphorylation; D011233:Precipitin Tests; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012329:RNA, Bacterial / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D012568:Schizosaccharomyces / Q000235:genetics; D029702:Schizosaccharomyces pombe Proteins; D012854:Sister Chromatid Exchange; D013997:Time Factors; D014960:X Chromosome; D014982:Xenopus laevis / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004278:DNA, Superhelical; D004268:DNA-Binding Proteins; D015801:Helminth Proteins; D006657:Histones; C110487:MIX-1 protein, C elegans; D046912:Multiprotein Complexes; C042027:RNA I; D012329:RNA, Bacterial; C409162:SMC4 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; C108312:condensin complexes; D064096:Aurora Kinase A; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; C576939:air-1 protein, C elegans; C491506:air-2 protein, C elegans; C576962:ark1 protein, S pombe; D000251:Adenosine Triphosphatases