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

Aurora B 特异性开关是防止中期/后期转变时不分离所必需的

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作者: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

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.

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