Aurora A and Aurora B jointly coordinate chromosome segregation and anaphase microtubule dynamics

Author:

Hégarat Nadia1,Smith Ewan1,Nayak Gowri12,Takeda Shunichi3,Eyers Patrick A.4,Hochegger Helfrid1

Affiliation:

1. Genome Damage and Stability Centre, University of Sussex, Brighton BN1 9RQ, England, UK

2. Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229

3. Department of Radiation Genetics, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan

4. Yorkshire Cancer Research Institute for Cancer Studies, School of Medicine, University of Sheffield, Sheffield S10 2RX, England, UK

Abstract

We established a conditional deletion of Aurora A kinase (AurA) in Cdk1 analogue-sensitive DT40 cells to analyze AurA knockout phenotypes after Cdk1 activation. In the absence of AurA, cells form bipolar spindles but fail to properly align their chromosomes and exit mitosis with segregation errors. The resulting daughter cells exhibit a variety of phenotypes and are highly aneuploid. Aurora B kinase (AurB)–inhibited cells show a similar chromosome alignment problem and cytokinesis defects, resulting in binucleate daughter cells. Conversely, cells lacking AurA and AurB activity exit mitosis without anaphase, forming polyploid daughter cells with a single nucleus. Strikingly, inhibition of both AurA and AurB results in a failure to depolymerize spindle microtubules (MTs) in anaphase after Cdk1 inactivation. These results suggest an essential combined function of AurA and AurB in chromosome segregation and anaphase MT dynamics.

Publisher

Rockefeller University Press

Subject

Cell Biology

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