Year: 2017
Type: article
Abstract: The centromere, a chromosomal locus that acts as a microtubule attachment site, is epigenetically specified by the enrichment of CENP-A nucleosomes. Centromere maintenance during the cell cycle requires HJURP-mediated CENP-A deposition, a process regulated by the Mis18 complex (Mis18α/Mis18β/Mis18BP1). Spatial and temporal regulation of Mis18 complex assembly is crucial for its centromere association and function. Here, we provide the molecular basis for the assembly and regulation of the Mis18 complex. We show that the N-terminal region of Mis18BP1 spanning amino acid residues 20-130 directly interacts with Mis18α/β to form the Mis18 complex. Within Mis18α/β, the Mis18α MeDiY domain can directly interact with Mis18BP1. Mis18α/β forms a hetero-hexamer with 4 Mis18α and 2 Mis18β. However, only two copies of Mis18BP1 interact with Mis18α/β to form a hetero-octameric assembly, highlighting the role of Mis18 oligomerization in limiting the number of Mis18BP1 within the Mis18 complex. Furthermore, we demonstrate the involvement of consensus Cdk1 phosphorylation sites on Mis18 complex assembly and thus provide a rationale for cell cycle-regulated timing of Mis18 assembly and CENP-A deposition.
Source: EMBO Reports
Institutions: Wellcome Centre for Cell Biology, University of Edinburgh
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,873
Awards: The Edinburgh Protein Production Facility (EPPF)., Proteomics at the Wellcome Trust Centre for Cell Biology., The Edinburgh Protein Production Facility (EPPF)., Molecular Mechanisms of Centromere Inheritance and Kinetochore Function, Molecular Mechanisms of Centromere Inheritance and Kinetochore Function, Structural Basis for the Molecular Mechanisms Involving the Ska Complex in Establishing Stable Kinetochore - Microtubule Attachments., Core funding renewal for the Wellcome Trust Centre for Cell Biology ., Structural basis for stable kinetochore-microtubule attachments and timely onset of anaphase by the Ska Complex., The role of non-histon proteins in chromosome structure and function during mitosis and apoptosis., The role of non-histone proteins in chromosome structure and function during mitosis., Core Funding for the Wellcome Trust Centre for Cell Biology
OpenAlex ID: W2604187656