Proper metaphase spindle length is determined by centromere proteins Mis12 and Mis6 required for faithful chromosome segregation.
High-fidelity chromosome transmission is fundamental in controlling the quality of the cell division cycle. The spindle pole-to-pole distance remains constant from metaphase to anaphase A. We show that fission yeast sister centromere-connecting proteins, Mis6 and Mis12, are required for correct spindle morphogenesis, determining metaphase spindle length. Thirty-five to sixty percent extension of metaphase spindle length takes place in mis6 and mis12 mutants. This may be due to incorrect spindle morphogenesis containing impaired sister centromeres or force unbalance between pulling by the linked sister kinetochores and kinetochore-independent pushing. The mutant spindle fully extends in anaphase, although it is accompanied by drastic missegregation by aberrant sister centromere separation. Hence, metaphase spindle length may be crucial for segregation fidelity. Suppressors of mis12 partly restore normal metaphase spindle length. In mis4 that is defective in sister chromatid cohesion, metaphase spindle length is also long, but anaphase spindle extension is blocked, probably due to the activated spindle checkpoint. Extensive missegregation is caused in mis12 only when Mis12 is inactivated from the previous M through to the following M, an effective way to avoid missegregation in the cell cycle. Mis12 has conserved homologs in budding yeast and filamentous fungi.
Core Research for Evolutional Science and Technology (CREST) Research Project, Department of Biophysics, Graduate School of Science, Kyoto University, Kitashirakawa-Oiwakecho, Sakyo-ku, Kyoto 606-8502 Japan.
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Goshima
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Saitoh
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Yanagida
D000595:Amino Acid Sequence; D000705:Anaphase; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D002455:Cell Division; D002503:Centromere / Q000737:chemistry / Q000648:ultrastructure*; D002842:Chromatids / Q000502:physiology; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology*; D018386:Kinetochores; D008677:Metaphase / Q000235:genetics*; D008969:Molecular Sequence Data; D009024:Morphogenesis; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D008941:Spindle Apparatus / Q000648:ultrastructure*
D018797:Cell Cycle Proteins; D005656:Fungal Proteins; C115842:MIS4 protein, S pombe; C120362:MTW1 protein, S cerevisiae; C107314:Mis6 protein, S pombe; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; C492315:mis12 protein, S pombe