HJURP Involvement in De Novo CenH3CENP-A and CENP-C Recruitment
Hiroaki Tachiwana,
Sebastian Müller,
Julia Blümer,
Kerstin Klare,
Andrea Musacchio,
Geneviève Almouzni
Affiliations
Hiroaki Tachiwana
Institut Curie, Centre de Recherche, Paris 75248, France
Sebastian Müller
Institut Curie, Centre de Recherche, Paris 75248, France
Julia Blümer
Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany Centre for Medical Biotechnology, Faculty of Biology, University of Duisburg-Essen, Essen 45141, Germany
Kerstin Klare
Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany Centre for Medical Biotechnology, Faculty of Biology, University of Duisburg-Essen, Essen 45141, Germany
Andrea Musacchio
Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany Centre for Medical Biotechnology, Faculty of Biology, University of Duisburg-Essen, Essen 45141, Germany
Geneviève Almouzni
Institut Curie, Centre de Recherche, Paris 75248, France
Although 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.
