Untangling the contribution of Haspin and Bub1 to Aurora B function during mitosis

Abstract

Hadders et al. demonstrate that the kinases Haspin and Bub1 recruit separate pools of Aurora B to centromeres of human cells. Surprisingly, the Haspin- and Bub1-dependent pools of Aurora B do not control phosphorylation of important kinetochore substrates nor the mitotic checkpoint.

Abstract

Aurora B kinase is essential for faithful chromosome segregation during mitosis. During (pro)metaphase, Aurora B is concentrated at the inner centromere by the kinases Haspin and Bub1. However, how Haspin and Bub1 collaborate to control Aurora B activity at centromeres remains unclear. Here, we show that either Haspin or Bub1 activity is sufficient to recruit Aurora B to a distinct chromosomal locus. Moreover, we identified a small, Bub1 kinase–dependent Aurora B pool that supported faithful chromosome segregation in otherwise unchallenged cells. Joined inhibition of Haspin and Bub1 activities fully abolished Aurora B accumulation at centromeres. While this impaired the correction of erroneous KT–MT attachments, it did not compromise the mitotic checkpoint, nor the phosphorylation of the Aurora B kinetochore substrates Hec1, Dsn1, and Knl1. This suggests that Aurora B substrates at the kinetochore are not phosphorylated by centromere-localized pools of Aurora B, and calls for a reevaluation of the current spatial models for how tension affects Aurora B–dependent kinetochore phosphorylation.