Mechanistic basis for Sgo1-mediated centromere localization and function of the CPC

Maria Alba Abad, Tanmay Gupta, Michael A Hadders, Amanda Meppelink, J Pepijn Wopken, Elizabeth Blackburn, Juan Zou, Anjitha Gireesh, Lana Buzuk, David A Kelly, Toni McHugh, Juri Rappsilber, Susanne M A Lens, A Arockia Jeyaprakash

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Abstract

Centromere association of the chromosomal passenger complex (CPC; Borealin-Survivin-INCENP-Aurora B) and Sgo1 is crucial for chromosome biorientation, a process essential for error-free chromosome segregation. Phosphorylated histone H3 Thr3 (H3T3ph; directly recognized by Survivin) and histone H2A Thr120 (H2AT120ph; indirectly recognized via Sgo1), together with CPC's intrinsic nucleosome-binding ability, facilitate CPC centromere recruitment. However, the molecular basis for CPC-Sgo1 binding and how their physical interaction influences CPC centromere localization are lacking. Here, using an integrative structure-function approach, we show that the "histone H3-like" Sgo1 N-terminal tail-Survivin BIR domain interaction acts as a hotspot essential for CPC-Sgo1 assembly, while downstream Sgo1 residues and Borealin contribute for high-affinity binding. Disrupting Sgo1-Survivin interaction abolished CPC-Sgo1 assembly and perturbed CPC centromere localization and function. Our findings reveal that Sgo1 and H3T3ph use the same surface on Survivin to bind CPC. Hence, it is likely that these interactions take place in a spatiotemporally restricted manner, providing a rationale for the Sgo1-mediated "kinetochore-proximal" CPC centromere pool.

Original languageEnglish
Article numbere202108156
Pages (from-to)1-22
JournalThe Journal of cell biology
Volume221
Issue number8
DOIs
Publication statusPublished - 1 Aug 2022

Keywords

  • Cell Cycle Proteins/genetics
  • Centromere/metabolism
  • Histones/genetics
  • Kinetochores/metabolism
  • Phosphorylation
  • Survivin/genetics

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