CODANIN-1 sequesters ASF1 by using a histone H3 mimic helix to regulate the histone supply.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 40038274.
- Also identified by DOI 10.1038/s41467-025-56976-7 and PMC identifier 11880193.
- Licence recorded as CC BY-NC-ND.
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Abstract
ASF1 is a major histone chaperone that regulates the supply of histone H3-H4 and facilitates nucleosome assembly to maintain chromatin structure during DNA replication and transcription. CODANIN-1 negatively regulates the function of ASF1. However, the molecular mechanism by which CODANIN-1 inhibits the ASF1-mediated histone supply remains elusive. Here, we present the cryo-EM structure of a human CODANIN-1_ASF1A complex at 3.75 Å resolution. The structure reveals that CODANIN-1 forms a dimer where each monomer holds two ASF1 molecules, utilizing two B-domains and two histone H3 mimic helices (HMHs). The interaction of CODANIN-1 with ASF1 via the HMH and B-domains inhibits the formation of an ASF1/H3-H4 complex and sequesters ASF1 in the cytoplasm. Our study provides a structural and molecular basis for the function of CODANIN-1 as negative regulator that highjacks ASF1 interaction sites with histones and downstream chaperones to inhibit nucleosome assembly.
Medical subject headings
- Histones
- Cell Cycle Proteins
- Molecular Chaperones