| Structural highlights
Function
[HIRA_HUMAN] Cooperates with ASF1A to promote replication-independent chromatin assembly. Required for the periodic repression of histone gene transcription during the cell cycle. Required for the formation of senescence-associated heterochromatin foci (SAHF) and efficient senescence-associated cell cycle exit.[1] [2] [3]
Publication Abstract from PubMed
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.
Functional activity of the H3.3 histone chaperone complex HIRA requires trimerization of the HIRA subunit.,Ray-Gallet D, Ricketts MD, Sato Y, Gupta K, Boyarchuk E, Senda T, Marmorstein R, Almouzni G Nat Commun. 2018 Aug 6;9(1):3103. doi: 10.1038/s41467-018-05581-y. PMID:30082790[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Nelson DM, Ye X, Hall C, Santos H, Ma T, Kao GD, Yen TJ, Harper JW, Adams PD. Coupling of DNA synthesis and histone synthesis in S phase independent of cyclin/cdk2 activity. Mol Cell Biol. 2002 Nov;22(21):7459-72. PMID:12370293
- ↑ Tagami H, Ray-Gallet D, Almouzni G, Nakatani Y. Histone H3.1 and H3.3 complexes mediate nucleosome assembly pathways dependent or independent of DNA synthesis. Cell. 2004 Jan 9;116(1):51-61. PMID:14718166
- ↑ Zhang R, Poustovoitov MV, Ye X, Santos HA, Chen W, Daganzo SM, Erzberger JP, Serebriiskii IG, Canutescu AA, Dunbrack RL, Pehrson JR, Berger JM, Kaufman PD, Adams PD. Formation of MacroH2A-containing senescence-associated heterochromatin foci and senescence driven by ASF1a and HIRA. Dev Cell. 2005 Jan;8(1):19-30. PMID:15621527 doi:S1534580704004083
- ↑ Ray-Gallet D, Ricketts MD, Sato Y, Gupta K, Boyarchuk E, Senda T, Marmorstein R, Almouzni G. Functional activity of the H3.3 histone chaperone complex HIRA requires trimerization of the HIRA subunit. Nat Commun. 2018 Aug 6;9(1):3103. doi: 10.1038/s41467-018-05581-y. PMID:30082790 doi:http://dx.doi.org/10.1038/s41467-018-05581-y
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