Although our understanding of centromere maintenance, marked by the histone H3 variant CenH3<sup>CENP-A</sup> 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<sup>CENP-A</sup> 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<sup>CENP-A</sup>: 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<sup>CENP-A</sup> and CENP-C recruitment.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)