Temporal and Spatial Regulation of Targeting Aurora B to the Inner Centromere

Abstract

Successful partitioning of chromosomes in mitosis relies on the bipolar attachment of sister chromatids at metaphase. For this biorientation, the chromosomal passenger complex (CPC), composed of catalytic kinase Aurora B and regulatory components (INCENP, Survivin, and Borealin), must be localized at the center of paired kinetochores, the site called the inner centromere. It is largely unknown what defines the inner centromere and how the CPC is targeted to this site. Recent studies point out that the shugoshin protein (SGO), originally identified as a cohesin protector, also acts as a conserved centromeric adapter of the CPC. Phosphorylation of the CPC by Cdk1 promotes direct binding with shugoshin, thus explaining how the CPC is targeted to the centromere in a timely manner at prometaphase during the cell cycle. Moreover, the phosphorylation of histone H3 threonine 3 (H3-pT3) mediated by Haspin cooperates with Bub1-mediated H2A-S121 phosphorylation in targeting the CPC to the inner centromere. H3-pT3 promotes nucleosome binding of Survivin, whereas H2A-pS121 facilitates the binding of shugoshin. Haspin colocalizes with cohesin by associating with Pds5, a cohesin-binding protein, and Bub1 localizes at kinetochores. Thus, the inner centromere is defined by the spatial intersection of two histone marks mediated by cohesin- and kinetochore-associated kinases.