HJURP is a cell-cycle-dependent maintenance and deposition factor of CENP-A at centromeres.
The histone H3 variant CenH3, called CENP-A in humans, is central in centromeric chromatin to ensure proper chromosome segregation. In the absence of an underlying DNA sequence, it is still unclear how CENP-A deposition at centromeres is determined. Here, we purified non-nucleosomal CENP-A complexes to identify direct CENP-A partners involved in such a mechanism and identified HJURP. HJURP was not detected in H3.1- or H3.3-containing complexes, indicating its specificity for CENP-A. HJURP centromeric localization is cell cycle regulated, and its transient appearance at the centromere coincides precisely with the proposed time window for new CENP-A deposition. Furthermore, HJURP downregulation leads to a major reduction in CENP-A at centromeres and impairs deposition of newly synthesized CENP-A, causing mitotic defects. We conclude that HJURP is a key factor for CENP-A deposition and maintenance at centromeres.
Dunleavy
Elaine M
EM
Laboratory of Nuclear Dynamics and Genome Plasticity, UMR CNRS/Institut Curie, Paris, France.
Roche
Danièle
D
Tagami
Hideaki
H
Lacoste
Nicolas
N
Ray-Gallet
Dominique
D
Nakamura
Yusuke
Y
Daigo
Yataro
Y
Nakatani
Yoshihiro
Y
Almouzni-Pettinotti
Geneviève
G
D001324:Autoantigens / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D002453:Cell Cycle / Q000502:physiology*; D002460:Cell Line; D002503:Centromere / Q000378:metabolism* / Q000648:ultrastructure; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D020090:Chromosome Segregation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D006657:Histones / Q000378:metabolism; D006801:Humans; D011485:Protein Binding
D001324:Autoantigens; C000619700:CENPA protein, human; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C524371:HJURP protein, human; D006657:Histones