Kinetochore-microtubule error correction is driven by differentially regulated interaction modes

Maria Kalantzaki, Etsushi Kitamura, Tongli Zhang, Akihisa Mino, Bele Novak, Tomoyuki U. Tanaka*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)421-+
Number of pages25
JournalNature Cell Biology
Volume17
Issue number4
Early online date9 Mar 2015
DOIs
Publication statusPublished - Apr 2015

Keywords

  • SPINDLE ASSEMBLY CHECKPOINT
  • CHROMOSOME BI-ORIENTATION
  • N-TERMINAL TAIL
  • AURORA-B
  • BUDDING YEAST
  • PLUS ENDS
  • MOLECULAR-MECHANISMS
  • RING COMPLEX
  • SKA COMPLEX
  • ATTACHMENT

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