Borealin-nucleosome interaction secures chromosome association of the chromosomal passenger complex.

Maria A Abad,Lana Buzuk,Jan G Ruppert,A Arockia Jeyaprakash,Martin Wear,William C Earnshaw,Juan Zou,Juri Rappsilber,Kim M Webb,David A Kelly,Philipp Voigt

doi:10.1083/jcb.201905040

Abstract

Chromosome association of the chromosomal passenger complex (CPC; consisting of Borealin, Survivin, INCENP, and the Aurora B kinase) is essential to achieve error-free chromosome segregation during cell division. Hence, understanding the mechanisms driving the chromosome association of the CPC is of paramount importance. Here using a multifaceted approach, we show that the CPC binds nucleosomes through a multivalent interaction predominantly involving Borealin. Strikingly, Survivin, previously suggested to target the CPC to centromeres, failed to bind nucleosomes on its own and requires Borealin and INCENP for its binding. Disrupting Borealin-nucleosome interactions excluded the CPC from chromosomes and caused chromosome congression defects. We also show that Borealin-mediated chromosome association of the CPC is critical for Haspin- and Bub1-mediated centromere enrichment of the CPC and works upstream of the latter. Our work thus establishes Borealin as a master regulator determining the chromosome association and function of the CPC.

Highlights

Chromosome segregation is a complex process involving numerous protein–protein and protein–DNA interactions tightly controlled by signaling networks consisting of kinases and phosphatases (Funabiki and Wynne, 2013; Gelens et al, 2018; Saurin, 2018)
Borealin nucleosome binding is essential for chromosome association of the chromosomal passenger complex (CPC) Consistent with our previous observations (Jeyaprakash et al, 2007), transient expression of a Myc-tagged Borealin lacking the first 9 aa and the C-terminal half (Myc-Borealin10–109) failed to rescue the siRNA-mediated depletion of endogenous Borealin, and the CPC was completely excluded from chromosomes during the early stages of mitosis, leading to chromosome congression defects (Fig. 1, A and B; and Fig. S1, A and B)
This led us to hypothesize a direct role for Borealin in mediating CPC– nucleosome interactions

Summary

Introduction

Chromosome segregation is a complex process involving numerous protein–protein and protein–DNA interactions tightly controlled by signaling networks consisting of kinases and phosphatases (Funabiki and Wynne, 2013; Gelens et al, 2018; Saurin, 2018). Chromosome association of the chromosomal passenger complex (CPC; consisting of Borealin, Survivin, INCENP, and the Aurora B kinase) is essential to achieve error-free chromosome segregation during cell division.

Results

Conclusion