Differential Binding Partners of the Mis18α/β YIPPEE Domains Regulate Mis18 Complex Recruitment to Centromeres

Cell Rep. 2016 Jun 7;15(10):2127-2135. doi: 10.1016/j.celrep.2016.05.004. Epub 2016 May 26.


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 Mis18α, Mis18β, and Mis18 binding protein 1 (Mis18BP1/hsKNL2). Although Mis18α and Mis18β 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 Mis18α directly interacts with the N terminus of Mis18BP1, whereas Mis18β 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 Mis18α 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.

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Cell Cycle
  • Cell Cycle Proteins
  • Centromere / metabolism*
  • Chromosomal Proteins, Non-Histone / chemistry
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Conserved Sequence
  • Cysteine / metabolism
  • HEK293 Cells
  • Humans
  • Protein Binding
  • Protein Domains


  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • MIS18A protein, human
  • MIS18BP1 protein, human
  • OIP5 protein, human
  • centromere protein C
  • Cysteine