Differential Binding Partners of the Mis18?/? YIPPEE Domains Regulate Mis18 Complex Recruitment to Centromeres.

ABSTRACT: The Mis18 complex specifies the site of new CENP-A nucleosome assembly by recruiting the CENP-A-specific assembly factor HJURP (Holliday junction recognition protein). The human Mis18 complex consists of Mis18?, Mis18?, and Mis18 binding protein 1 (Mis18BP1/hsKNL2). Although Mis18? and Mis18? are highly homologous proteins, we find that their conserved YIPPEE domains mediate distinct interactions that are essential to link new CENP-A deposition to existing centromeres. We find that Mis18? directly interacts with the N terminus of Mis18BP1, whereas Mis18? directly interacts with CENP-C during G1 phase, revealing that these proteins have evolved to serve distinct functions in centromeres of higher eukaryotes. The N terminus of Mis18BP1, containing both the Mis18? and CENP-C binding domains, is necessary and sufficient for centromeric localization. Therefore, the Mis18 complex contains dual CENP-C recognition motifs that are combinatorially required to generate robust centromeric localization that leads to CENP-A deposition.

SUBMITTER: Stellfox ME 

PROVIDER: S-EPMC4899240 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature