HJURP involvement in de novo CenH3(CENP-A) and CENP-C recruitment

• Published in: Cell reports (Cambridge) Vol. 11; no. 1; pp. 22 - 32
• Main Authors: Tachiwana, Hiroaki, Müller, Sebastian, Blümer, Julia, Klare, Kerstin, Musacchio, Andrea, Almouzni, Geneviève
• Format: Journal Article
• Language: English
• Published: United States 07.04.2015
• Subjects: Autoantigens - genetics; Autoantigens - metabolism; Centromere - genetics; Centromere Protein A; Chromosomal Proteins, Non-Histone - genetics; Chromosomal Proteins, Non-Histone - metabolism; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Histones - genetics; Humans; Kinetochores - metabolism; Molecular Chaperones - genetics; Nucleosomes - genetics; Protein Binding - genetics
• DOI: 10.1016/j.celrep.2015.03.013

Although our understanding of centromere maintenance, marked by the histone H3 variant CenH3(CENP-A) in most eukaryotes, has progressed, the mechanism underlying the de novo formation of centromeres remains unclear. We used a synthetic system to dissect how CenH3(CENP-A) contributes to the accumulation of CENP-C and CENP-T, two key components that are necessary for the formation of functional kinetochores. We find that de novo CENP-T accumulation depends on CENP-C and that recruitment of these factors requires two domains in CenH3(CENP-A): the HJURP-binding region (CATD) and the CENP-C-binding region (CAC). Notably, HJURP interacts directly with CENP-C and is critical for de novo accumulation of CENP-C at synthetic centromeres. On the basis of our findings, we propose that HJURP serves a dual chaperone function in coordinating CenH3(CENP-A) and CENP-C recruitment.