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.