Functional activity of the H3.3 histone chaperone complex HIRA requires trimerization of the HIRA subunit.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30082790.
- Also identified by DOI 10.1038/s41467-018-05581-y and PMC identifier 6078998.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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.
Medical subject headings
- Adaptor Proteins, Signal Transducing
- Cell Cycle Proteins
- DNA
- Histone Chaperones
- Histones
- Molecular Chaperones
- Nuclear Proteins
- Transcription Factors