CODANIN-1 sequesters ASF1 by using a histone H3 mimic helix to regulate the histone supply
Guardado en:
| Publicado en: | bioRxiv (Feb 7, 2025) |
|---|---|
| Autor principal: | |
| Otros Autores: | , , , |
| Publicado: |
Cold Spring Harbor Laboratory Press
|
| Materias: | |
| Acceso en línea: | Citation/Abstract Full text outside of ProQuest |
| Etiquetas: |
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| Resumen: | AbstractASF1 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 electron microscopy (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 a unique negative regulator that highjacks ASF1 interaction sites with histones and downstream chaperones to inhibit nucleosome assembly.Competing Interest StatementJ.S. is a CTO of Epinogen. A.G. is a co-founder and CSO of Ankrin Therapeutics.Footnotes* We included a new structure of the complex and its biochemical analysis |
|---|---|
| ISSN: | 2692-8205 |
| DOI: | 10.1101/2024.07.10.602876 |
| Fuente: | Biological Science Database |