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The Aurora B specificity switch is required to protect from non-disjunction at the metaphase/anaphase transition

Author

Listed:
  • Joanna R. Kelly

    (Francis Crick Institute
    Cancer Research UK, Manchester Institute)

  • Silvia Martini

    (Francis Crick Institute)

  • Nicola Brownlow

    (Francis Crick Institute
    Instituto de Neurociencias)

  • Dhira Joshi

    (Francis Crick Institute)

  • Stefania Federico

    (Francis Crick Institute)

  • Shirin Jamshidi

    (King’s College London)

  • Svend Kjaer

    (Francis Crick Institute)

  • Nicola Lockwood

    (Francis Crick Institute)

  • Khondaker Miraz Rahman

    (King’s College London)

  • Franca Fraternali

    (King’s College London)

  • Peter J. Parker

    (Francis Crick Institute
    King’s College London)

  • Tanya N. Soliman

    (Francis Crick Institute
    Barts Cancer Institute, Queen Mary University London)

Abstract

The Aurora B abscission checkpoint delays cytokinesis until resolution of DNA trapped in the cleavage furrow. This process involves PKCε phosphorylation of Aurora B S227. Assessing if this PKCε-Aurora B module provides a more widely exploited genome-protective control for the cell cycle, we show Aurora B phosphorylation at S227 by PKCε also occurs during mitosis. Expression of Aurora B S227A phenocopies inhibition of PKCε in by-passing the delay and resolution at anaphase entry that is associated with non-disjunction and catenation of sister chromatids. Implementation of this anaphase delay is reflected in PKCε activation following cell cycle dependent cleavage by caspase 7; knock-down of caspase 7 phenocopies PKCε loss, in a manner rescued by ectopically expressing/generating a free PKCε catalytic domain. Molecular dynamics indicates that Aurora B S227 phosphorylation induces conformational changes and this manifests in a profound switch in specificity towards S29 TopoIIα phosphorylation, a response necessary for catenation resolution during mitosis.

Suggested Citation

  • Joanna R. Kelly & Silvia Martini & Nicola Brownlow & Dhira Joshi & Stefania Federico & Shirin Jamshidi & Svend Kjaer & Nicola Lockwood & Khondaker Miraz Rahman & Franca Fraternali & Peter J. Parker & , 2020. "The Aurora B specificity switch is required to protect from non-disjunction at the metaphase/anaphase transition," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15163-6
    DOI: 10.1038/s41467-020-15163-6
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    Cited by:

    1. Silvia Martini & Khalil Davis & Rupert Faraway & Lisa Elze & Nicola Lockwood & Andrew Jones & Xiao Xie & Neil Q. McDonald & David J. Mann & Alan Armstrong & Jernej Ule & Peter J. Parker, 2021. "A genetically-encoded crosslinker screen identifies SERBP1 as a PKCε substrate influencing translation and cell division," Nature Communications, Nature, vol. 12(1), pages 1-16, December.

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