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; Tanya N. Soliman

doi:10.1038/s41467-020-15163-6

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, Tanya N. Soliman

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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.

Original language	English
Article number	1396
Pages (from-to)	1-14
Journal	Nature Communications
Volume	11
Early online date	13 Mar 2020
DOIs	https://doi.org/10.1038/s41467-020-15163-6
Publication status	Published - 13 Mar 2020

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The Aurora B specificity_KELLY_Accepted13Feb2020_GOLD VoRFinal published version, 4.43 MBLicence: CC BY

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Kelly, J. R., Martini, S., Brownlow, N., Joshi, D., Federico, S., Jamshidi, S., Kjaer, S., Lockwood, N., Rahman, K. M., Fraternali, F., Parker, P. J., & Soliman, T. N. (2020). The Aurora B specificity switch is required to protect from non-disjunction at the metaphase/anaphase transition. Nature Communications, 11, 1-14. Article 1396. https://doi.org/10.1038/s41467-020-15163-6

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

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.",

author = "Kelly, {Joanna R.} and Silvia Martini and Nicola Brownlow and Dhira Joshi and Stefania Federico and Shirin Jamshidi and Svend Kjaer and Nicola Lockwood and Rahman, {Khondaker Miraz} and Franca Fraternali and Parker, {Peter J.} and Soliman, {Tanya N.}",

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AU - Joshi, Dhira

AU - Federico, Stefania

AU - Jamshidi, Shirin

AU - Kjaer, Svend

AU - Lockwood, Nicola

AU - Rahman, Khondaker Miraz

AU - Fraternali, Franca

AU - Parker, Peter J.

AU - Soliman, Tanya N.

PY - 2020/3/13

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N2 - 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.

AB - 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.

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

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