Small changes in phospho-occupancy at the kinetochore-microtubule interface drive mitotic fidelity

Thomas J. Kucharski, Rufus Hards, Sarah E. Vandal, Maria Alba Abad, A. Arockia Jeyaprakash, Edward Kaye, Aymen Al-Rawi, Tony Ly, Kristina M. Godek, Scott A. Gerber, Duane A. Compton (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    4 Citations (Scopus)
    118 Downloads (Pure)

    Abstract

    Kinetochore protein phosphorylation promotes the correction of erroneous microtubule attachments to ensure faithful chromosome segregation during cell division. Determining how phosphorylation executes error correction requires an understanding of whether kinetochore substrates are completely (i.e., all-or-none) or only fractionally phosphorylated. Using quantitative mass spectrometry (MS), we measured phospho-occupancy on the conserved kinetochore protein Hec1 (NDC80) that directly binds microtubules. None of the positions measured exceeded ∼50% phospho-occupancy, and the cumulative phospho-occupancy changed by only ∼20% in response to changes in microtubule attachment status. The narrow dynamic range of phospho-occupancy is maintained, in part, by the ongoing phosphatase activity. Further, both Cdk1-Cyclin B1 and Aurora kinases phosphorylate Hec1 to enhance error correction in response to different types of microtubule attachment errors. The low inherent phospho-occupancy promotes microtubule attachment to kinetochores while the high sensitivity of kinetochore-microtubule attachments to small changes in phospho-occupancy drives error correction and ensures high mitotic fidelity.

    Original languageEnglish
    Article numbere202107107
    Number of pages33
    JournalJournal of Cell Biology
    Volume221
    Issue number9
    Early online date25 Jul 2022
    DOIs
    Publication statusPublished - 5 Sept 2022

    Keywords

    • Aurora Kinases/metabolism
    • CDC2 Protein Kinase/metabolism
    • Chromosome Segregation
    • Cyclin B1/metabolism
    • Cytoskeletal Proteins/metabolism
    • HeLa Cells
    • Humans
    • Kinetochores/metabolism
    • Microtubules/metabolism
    • Mitosis
    • Phosphorylation

    ASJC Scopus subject areas

    • Cell Biology

    Fingerprint

    Dive into the research topics of 'Small changes in phospho-occupancy at the kinetochore-microtubule interface drive mitotic fidelity'. Together they form a unique fingerprint.

    Cite this