title: Two kinesin-like Kin I family proteins in fission yeast regulate the establishment of metaphase and the onset of anaphase A.
abstract: BACKGROUND
  Metaphase is thought to be a force-equilibrium state of "tug of war," in which poleward forces are pulling kinetochores and counteracting the cohesive forces between the centromeres. Unlike conventional kinesins, members of the Kin I family are microtubule-depolymerizing enzymes, which are expected to be molecules that could generate poleward forces.
  
  
  RESULTS
  We have characterized mitotic roles of two Kin I homologs, Klp5 and Klp6, in fission yeast. Klp5 and Klp6 colocalize to the mitotic kinetochores and the spindle midzone. These two proteins form a heterocomplex, but not a homocomplex. Albeit not essential, both proteins are required for accurate chromosome segregation and normal morphology of interphase microtubules. Time-lapse live analysis using GFP-alpha-tubulin indicates that these mutants spend a much longer time (2-fold) in mitosis before the initiation of anaphase B. Further observation using kinetochore and centromere markers shows that, in these mutants, sister centromeres move back and forth between the two poles, indicating that entry into anaphase A is delayed. This is supported by live image analysis showing that Cut2 securin is retained during the prolonged mitosis. Furthermore, the mitotic extension is dependent upon the Mad2 spindle checkpoint.
  
  
  CONCLUSIONS
  We discuss two models of Kin I function in fission yeast. One proposes that Klp5 and Klp6 are required for efficient capturing of kinetochores by the spindles, while the other proposes that they are required to generate tension upon kinetochore capturing. Kin I, therefore, plays a fundamental role in the establishment of metaphase, probably by generating poleward forces at the kinetochores.
authors.affiliation: Laboratory of Cell Regulation, Cancer Research UK, London Research Institute, PO Box 123, 44 Lincoln's Inn Fields, WC2A 3PX, London, United Kingdom.
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Garcia
authors.forename: Nirada
authors.initials: N
authors.lastname: Koonrugsa
authors.forename: Takashi
authors.initials: T
authors.lastname: Toda
mesh_terms: D000705:Anaphase; D000782:Aneuploidy; D001483:Base Sequence; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D016547:Kinesins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018386:Kinetochores / Q000378:metabolism; D064246:Mad2 Proteins; D008677:Metaphase; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000378:metabolism; D009687:Nuclear Proteins; D012568:Schizosaccharomyces / Q000166:cytology* / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D064249:Securin; D008941:Spindle Apparatus / Q000378:metabolism; D013997:Time Factors
chemical_list: D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D005656:Fungal Proteins; C090556:KLP68D protein, Drosophila; D064246:Mad2 Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D029702:Schizosaccharomyces pombe Proteins; D064249:Securin; C577696:mad2 protein, S pombe; C459102:Klp6 protein, S pombe; D016547:Kinesins