Kinetochore-microtubule error correction is driven by differentially regulated interaction modes.
For proper chromosome segregation, sister kinetochores must interact with microtubules from opposite spindle poles (bi-orientation). To establish bi-orientation, aberrant kinetochore-microtubule attachments are disrupted (error correction) by aurora B kinase (Ipl1 in budding yeast). Paradoxically, during this disruption, new attachments are still formed efficiently to enable fresh attempts at bi-orientation. How this is possible remains an enigma. Here we show that kinetochore attachment to the microtubule lattice (lateral attachment) is impervious to aurora B regulation, but attachment to the microtubule plus end (end-on attachment) is disrupted by this kinase. Thus, a new lateral attachment is formed without interference, then converted to end-on attachment and released if incorrect. This process continues until bi-orientation is established and stabilized by tension across sister kinetochores. We reveal how aurora B specifically promotes disruption of the end-on attachment through phospho-regulation of kinetochore components Dam1 and Ndc80. Our results reveal fundamental mechanisms for promoting error correction for bi-orientation.
Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dow Street Dundee DD1 5EH, UK.
Maria
M
Kalantzaki
Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dow Street Dundee DD1 5EH, UK.
Etsushi
E
Kitamura
Oxford Centre for Integrative Systems Biology, Department of Biochemistry, University of Oxford, South Parks Road Oxford OX1 3QU, UK.
Tongli
T
Zhang
Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dow Street Dundee DD1 5EH, UK.
Akihisa
A
Mino
Oxford Centre for Integrative Systems Biology, Department of Biochemistry, University of Oxford, South Parks Road Oxford OX1 3QU, UK.
Béla
B
Novák
Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dow Street Dundee DD1 5EH, UK.
Tomoyuki U
TU
Tanaka
D064127:Aurora Kinases / Q000235:genetics; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000235:genetics*; D020090:Chromosome Segregation / Q000235:genetics; D018386:Kinetochores / Q000502:physiology*; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008870:Microtubules / Q000502:physiology*; D008938:Mitosis; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D008941:Spindle Apparatus / Q000502:physiology
C066503:CDC6 protein, S cerevisiae; D018797:Cell Cycle Proteins; C116003:DAM1 protein, S cerevisiae; D008869:Microtubule-Associated Proteins; C112472:NDC80 protein, S cerevisiae; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D064127:Aurora Kinases; C576961:IPL1 protein, S cerevisiae