The Aurora B specificity switch is required to protect from non-disjunction at the metaphase/anaphase transition
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Joanna R Kelly Silvia Martini Nicola Brownlow Dhira Joshi Stefania Federico Shirin Jamshidi Svend Kjaer Nicola Lockwood Khondaker Miraz Rahman Franca Fraternali Peter Parker Tanya SolimanAbstract
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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Publisher website (DOI) 10.1038/s41467-020-15163-6
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Europe PubMed Central 32170202
Pubmed 32170202
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