Essentiality of CENP-A depends on its binding mode to HJURP

Journal Cell Reports (2020)
Title Essentiality of CENP-A depends on its binding mode to HJURP
Laboratory Laboratory of Chromosome Biology〈Prof. FUKAGAWA Tatsuo〉

CENP-A incorporation is critical for centromere specification and is mediated by its chaperone HJURP. The CENP-A-targeting-domain (CATD) of CENP-A specifically binds to HJURP and this binding itself is conserved. However, critical residues of CENP-A vary between species, and the binding interface of CENP-A–HJURP is yet to be understood. Here, we identified the critical residues for chicken CENP-A or HJURP. Interestingly, the A59Q mutation in the α1-helix of chicken CENP-A caused CENP-A mis-incorporation and subsequent cell death, while the corresponding mutation in human CENP-A (S68Q) did not. We also found that W53 of HJURP, which is a contact site of A59 in CENP-A, is also essential in chicken cells. Our comprehensive analyses revealed that the affinity of human HJURP to CATD is strong enough even with the CENP-A α1-helix mutation, but this is not the case in chicken. However, introduction of two arginine residues to the chicken HJURP αA-helix suppressed the CENP-A mis-incorporation in chicken cells expressing CENP-AA59Q. Our data explain the mechanisms and evolution of CENP-A essentiality via CENP-A–HJURP interaction.


Tetsuya Hori (1), JingHui Cao (1), Kohei Nishimura (1), Mariko Ariyoshi (1), Yasuhiro Arimura (2), Hitoshi Kurumizaka (2), Tatsuo Fukagawa (1)

  1. Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan.
  2. Laboratory of Chromatin Structure and Function, Institute for Quantitative Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
PubMed 33207191