Condensin association with histone H2A shapes mitotic chromosomes

• Published in: Nature (London) 2011-06, Vol.474 (7352), p.477-483
• Main Authors: Tada, Kenji, Susumu, Hiroaki, Sakuno, Takeshi, Watanabe, Yoshinori
• Format: Article
• Language: English
• Subjects: 631/80/641/1655; 631/80/641/2358; Adenosine Triphosphatases - metabolism; Aurora Kinase B; Aurora Kinases; Binding Sites; Biological and medical sciences; cdc25 Phosphatases - genetics; cdc25 Phosphatases - metabolism; Cell Cycle Proteins - metabolism; Cell cycle, cell proliferation; Cell physiology; Chromatin; Chromatin - metabolism; Chromosomal Proteins, Non-Histone - metabolism; Chromosomes; Chromosomes, Fungal - metabolism; DNA-Binding Proteins - metabolism; Fundamental and applied biological sciences. Psychology; Genetic aspects; Genetics; HeLa Cells; Histones; Histones - metabolism; Humanities and Social Sciences; Humans; Kinetochores - metabolism; Microtubules - metabolism; Mitosis; Molecular and cellular biology; multidisciplinary; Multiprotein Complexes - metabolism; Mutation; Nuclear Proteins - metabolism; Phosphorylation; Physiological aspects; Protein Binding; Protein Transport; Protein-Serine-Threonine Kinases - metabolism; Saccharomyces cerevisiae; Schizosaccharomyces - cytology; Schizosaccharomyces - metabolism; Schizosaccharomyces pombe; Schizosaccharomyces pombe Proteins - metabolism; Science; Studies; Yeast; Yeasts
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature10179

Chromosome structure is dynamically regulated during cell division, and this regulation is dependent, in part, on condensin. The localization of condensin at chromosome arms is crucial for chromosome partitioning during anaphase. Condensin is also enriched at kinetochores but its precise role and loading machinery remain unclear. Here we show that fission yeast ( Schizosaccharomyces pombe ) kinetochore proteins Pcs1 and Mde4—homologues of budding yeast ( Saccharomyces cerevisiae ) monopolin subunits and known to prevent merotelic kinetochore orientation—act as a condensin ‘recruiter’ at kinetochores, and that condensin itself may act to clamp microtubule binding sites during metaphase. In addition to the regional recruitment factors, overall condensin association with chromatin is governed by the chromosomal passenger kinase Aurora B. Aurora-B-dependent phosphorylation of condensin promotes its association with histone H2A and H2A.Z, which we identify as conserved chromatin ‘receptors’ of condensin. Condensin phosphorylation and its deposition onto chromosome arms reach a peak during anaphase, when Aurora B kinase relocates from centromeres to the spindle midzone, where the separating chromosome arms are positioned. Our results elucidate the molecular basis for the spatiotemporal regulation of mitotic chromosome architecture, which is crucial for chromosome partitioning. Recruiting condensin During mitosis, chromosomes are made compact and rigid by the action of condensin. This protein is thought to have different roles in the chromosome arms and at the kinetochore, but how it is localized to these regions is unclear. Tada et al . show that the kinetochore protein monopolin is a recruiter for centromeric condensin. In addition, phosphorylation by Aurora B kinase promotes condensin binding to certain histones. Aurora B localization varies through the cell cycle, which may account for cell-cycle-linked recruitment of condensin at the kinetochore.