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Title

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

AuthorsKelly, Joanna R.; Martini, Silvia; Brownlow, Nicola; Joshi, Dhira; Federico, Stefania; Jamshidi, Shirin; Kjaer, Svend; Lockwood, Nicola; Miraz Rahman, Khondaker; Fraternali, Franca; Parker, Peter J.; Soliman, Tanya N.
Issue Date2020
PublisherSpringer Nature
CitationNature Communications 11: 1396 (2020)
AbstractThe 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.
Publisher version (URL)https://doi.org/10.1038/s41467-020-15163-6
URIhttp://hdl.handle.net/10261/217971
DOIhttp://dx.doi.org/10.1038/s41467-020-15163-6
E-ISSN2041-1723
Appears in Collections:(IN) Artículos
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