10779/crick.11993928.v1 Joanna R Kelly Joanna R Kelly Silvia Martini Silvia Martini Nicola Brownlow Nicola Brownlow Dhira Joshi Dhira Joshi Stefania Federico Stefania Federico Shirin Jamshidi Shirin Jamshidi Svend Kjaer Svend Kjaer Nicola Lockwood Nicola Lockwood Khondaker Miraz Rahmen Khondaker Miraz Rahmen Franca Fraternali Franca Fraternali Peter J Parker Peter J Parker Tanya N Soliman Tanya N Soliman The Aurora B specificity switch is required to protect from non-disjunction at the metaphase/anaphase transition. The Francis Crick Institute 2020 Parker FC001130 PC SB LM-ack 2020-04-17 11:00:14 Journal contribution https://crick.figshare.com/articles/journal_contribution/The_Aurora_B_specificity_switch_is_required_to_protect_from_non-disjunction_at_the_metaphase_anaphase_transition_/11993928 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.