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

60 Pages Posted: 2 Mar 2020 Publication Status: Review Complete

See all articles by Tetsuya Hori

Tetsuya Hori

Osaka University - Graduate School of Frontier Biosciences

JingHui Cao

Osaka University - Graduate School of Frontier Biosciences

Kohei Nishimura

Osaka University - Graduate School of Frontier Biosciences

Mariko Ariyoshi

Osaka University - Graduate School of Frontier Biosciences

Yasuhiro Arimura

University of Tokyo - Laboratory of Chromatin Structure and Function

Hitoshi Kurumizaka

University of Tokyo - Laboratory of Chromatin Structure and Function

Tatsuo Fukagawa

Osaka University - Graduate School of Frontier Biosciences

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Abstract

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.

Keywords: Centromere, CENP-A, HJURP, Histone chaperone

Suggested Citation

Hori, Tetsuya and Cao, JingHui and Nishimura, Kohei and Ariyoshi, Mariko and Arimura, Yasuhiro and Kurumizaka, Hitoshi and Fukagawa, Tatsuo, Essentiality of CENP-A Depends on Its Binding Mode to HJURP. Available at SSRN: https://ssrn.com/abstract=3544132 or http://dx.doi.org/10.2139/ssrn.3544132
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Tetsuya Hori

Osaka University - Graduate School of Frontier Biosciences ( email )

Japan

JingHui Cao

Osaka University - Graduate School of Frontier Biosciences

Japan

Kohei Nishimura

Osaka University - Graduate School of Frontier Biosciences

Japan

Mariko Ariyoshi

Osaka University - Graduate School of Frontier Biosciences

Japan

Yasuhiro Arimura

University of Tokyo - Laboratory of Chromatin Structure and Function

Tokyo, 113-0032
Japan

Hitoshi Kurumizaka

University of Tokyo - Laboratory of Chromatin Structure and Function

Tokyo, 113-0032
Japan

Tatsuo Fukagawa (Contact Author)

Osaka University - Graduate School of Frontier Biosciences ( email )

Japan

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