TY - JOUR
T1 - Functional activity of the H3.3 histone chaperone complex HIRA requires trimerization of the HIRA subunit
AU - Ray-Gallet, Dominique
AU - Ricketts, M. Daniel
AU - Sato, Yukari
AU - Gupta, Kushol
AU - Boyarchuk, Ekaterina
AU - Senda, Toshiya
AU - Marmorstein, Ronen
AU - Almouzni, Geneviève
N1 - Funding Information:
This work was supported by la Ligue Nationale contre le Cancer (Equipe labellisée Ligue), ANR-11-LABX-0044_DEEP and ANR-10-IDEX-0001-02 PSL, ANR-12-BSV5-0022-02 “CHAPINHIB”, ANR-14-CE16-0009 “Epicure”, ANR-14-CE10-0013 “CEL-LECTCHIP”, EU project 678563 “EPOCH28”, ERC-2015-ADG-694694 “ChromA-DICT”, ANR-16-CE15-0018 “CHRODYT”, ANR-16-CE12-0024 “CHIFT” and ANR-16-CE11-0028 “REPLICAF”, and “Parisian Alliance of Cancer Research Institutes—PACRI”. This work was also supported by the National Institutes of Health grants AG031862 to R. M. and an American Heart Association predoctoral fellowship 12PRE12030157 to M.D. R. and JSPS KAKENHI 16K14908 to Y.S. and Platform for Drug Discovery, Informatics and Structural Life Science, and Basis for Supporting Innovative Drug Discovery and Life Science Research by AMED (Japan) to T.S. The synchrotron radiation experiments were performed with the approval of the Japan Synchrotron Radiation Research Institute (JASRI) (proposal no. 2015B1049 and 2016A2749) and the Photon Factory Program Advisory Committee (proposal no. 2015G122). We thank H. Okumura (JASRI) for technical help in the use of beamline BL41XU, T. Ota (KEK) for technical assistance and I. Simeonova for statistical analysis help.
Publisher Copyright:
© 2018, The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - The HIRA histone chaperone complex deposits the histone variant H3.3 onto chromatin in a DNA synthesis-independent manner. It comprises three identified subunits, HIRA, UBN1 and CABIN1, however the functional oligomerization state of the complex has not been investigated. Here we use biochemical and crystallographic analysis to show that the HIRA subunit forms a stable homotrimer that binds two subunits of CABIN1 in vitro. A HIRA mutant that is defective in homotrimer formation interacts less efficiently with CABIN1, is not enriched at DNA damage sites upon UV irradiation and cannot rescue new H3.3 deposition in HIRA knockout cells. The structural homology with the homotrimeric replisome component Ctf4/AND-1 enables the drawing of parallels and discussion of the functional importance of the homotrimerization state of the HIRA subunit.
AB - The HIRA histone chaperone complex deposits the histone variant H3.3 onto chromatin in a DNA synthesis-independent manner. It comprises three identified subunits, HIRA, UBN1 and CABIN1, however the functional oligomerization state of the complex has not been investigated. Here we use biochemical and crystallographic analysis to show that the HIRA subunit forms a stable homotrimer that binds two subunits of CABIN1 in vitro. A HIRA mutant that is defective in homotrimer formation interacts less efficiently with CABIN1, is not enriched at DNA damage sites upon UV irradiation and cannot rescue new H3.3 deposition in HIRA knockout cells. The structural homology with the homotrimeric replisome component Ctf4/AND-1 enables the drawing of parallels and discussion of the functional importance of the homotrimerization state of the HIRA subunit.
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U2 - 10.1038/s41467-018-05581-y
DO - 10.1038/s41467-018-05581-y
M3 - Article
C2 - 30082790
AN - SCOPUS:85051103841
SN - 2041-1723
VL - 9
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 3103
ER -