The Aurora B specificity switch is required to protect from non-disjunction at the metaphase/anaphase transition
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 () and
Tanya N. Soliman ()
Additional contact information
Joanna R. Kelly: Francis Crick Institute
Silvia Martini: Francis Crick Institute
Nicola Brownlow: Francis Crick Institute
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
Tanya N. Soliman: Francis Crick Institute
Nature Communications, 2020, vol. 11, issue 1, 1-14
Abstract:
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.
Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15163-6
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DOI: 10.1038/s41467-020-15163-6
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