HJURP Involvement in De Novo CenH3CENP-A and CENP-C Recruitment

• De novo CENP-T accumulation at an ectopic locus depends on CENP-C
• Two distinct domains in CenH3CENP-A are necessary for de novo CENP-C accumulation
• CENP-C recruitment entails a direct interaction between CENP-C and HJURP
• HJURP is involved in recruiting CENP-C at synthetic centromeres

SummaryAlthough our understanding of centromere maintenance, marked by the histone H3 variant CenH3CENP-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 CenH3CENP-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 CenH3CENP-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 CenH3CENP-A and CENP-C recruitment.

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