Posttranslational modifications of CENP-A: marks of distinction

Chromosoma. 2018 Sep;127(3):279-290. doi: 10.1007/s00412-018-0665-x. Epub 2018 Mar 22.

Abstract

Centromeres are specialized chromosome domain that serve as the site for kinetochore assembly and microtubule attachment during cell division, to ensure proper segregation of chromosomes. In higher eukaryotes, the identity of active centromeres is marked by the presence of CENP-A (centromeric protein-A), a histone H3 variant. CENP-A forms a centromere-specific nucleosome that acts as a foundation for centromere assembly and function. The posttranslational modification (PTM) of histone proteins is a major mechanism regulating the function of chromatin. While a few CENP-A site-specific modifications are shared with histone H3, the majority are specific to CENP-A-containing nucleosomes, indicating that modification of these residues contribute to centromere-specific function. CENP-A undergoes posttranslational modifications including phosphorylation, acetylation, methylation, and ubiquitylation. Work from many laboratories have uncovered the importance of these CENP-A modifications in its deposition at centromeres, protein stability, and recruitment of the CCAN (constitutive centromere-associated network). Here, we discuss the PTMs of CENP-A and their biological relevance.

Keywords: CENP-A; Centromere; Chromatin; Kinetochore; Mitosis; Posttranslational modification.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Cycle
  • Centromere / genetics
  • Centromere / metabolism
  • Centromere Protein A / chemistry
  • Centromere Protein A / metabolism*
  • Histones / metabolism
  • Humans
  • Methylation
  • Mitosis / genetics
  • Protein Binding
  • Protein Processing, Post-Translational*
  • Species Specificity
  • Structure-Activity Relationship

Substances

  • Centromere Protein A
  • Histones