Essentiality of CENP-A Depends on Its Binding Mode to HJURP

Cell Reports

JingHui Cao¹  Tetsuya Hori²  Mariko Ariyoshi²  Yasuhiro Arimura²  Kohei Nishimura²  Hitoshi Kurumizaka³  Tatsuo Fukagawa³ 

[1] Corresponding author;Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan;Laboratory of Chromatin Structure and Function, Institute for Quantitative Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan;

关键词: centromere;    CENP-A;    HJURP;    histone chaperone;    kinetochore;    mitosis;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: CENP-A incorporation is critical for centromere specification and is mediated by the chaperone HJURP. The CENP-A-targeting domain (CATD) of CENP-A specifically binds to HJURP, and this binding is conserved. However, the binding interface of CENP-A-HJURP is yet to be understood. Here, we identify the critical residues for chicken CENP-A or HJURP. The A59Q mutation in the α1-helix of chicken CENP-A causes CENP-A mis-incorporation and subsequent cell death, whereas the corresponding mutation in human CENP-A does not. We also find that W53 of HJURP, which is a contact site of A59 in CENP-A, is also essential in chicken cells. Our comprehensive analyses reveal that the affinities of HJURP to CATD differ between chickens and humans. However, the introduction of two arginine residues to the chicken HJURP αA-helix suppresses CENP-A mis-incorporation in chicken cells expressing CENP-AA59Q. Our data explain the mechanisms and evolution of CENP-A essentiality by the CENP-A-HJURP interaction.

【 授权许可】

Unknown