8YV8
Cryo-EM structure of CDCA7 bound to nucleosome including hemimethylated CpG site in Widom601 positioning sequence.
Summary for 8YV8
| Entry DOI | 10.2210/pdb8yv8/pdb |
| EMDB information | 39594 |
| Descriptor | Histone H3.1, Histone H4, Histone H2A type 1-B/E, ... (8 entities in total) |
| Functional Keywords | nucleosome, dna methylation, cdca7, dna binding protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 11 |
| Total formula weight | 210859.56 |
| Authors | Kikuchi, A.,Shikimachi, R.,Nishiyama, A.,Funabiki, H.,Arita, K. (deposition date: 2024-03-28, release date: 2024-07-31, Last modification date: 2025-03-12) |
| Primary citation | Wassing, I.E.,Nishiyama, A.,Shikimachi, R.,Jia, Q.,Kikuchi, A.,Hiruta, M.,Sugimura, K.,Hong, X.,Chiba, Y.,Peng, J.,Jenness, C.,Nakanishi, M.,Zhao, L.,Arita, K.,Funabiki, H. CDCA7 is an evolutionarily conserved hemimethylated DNA sensor in eukaryotes. Sci Adv, 10:eadp5753-eadp5753, 2024 Cited by PubMed Abstract: Mutations of the SNF2 family ATPase HELLS and its activator CDCA7 cause immunodeficiency, centromeric instability, and facial anomalies syndrome, characterized by DNA hypomethylation at heterochromatin. It remains unclear why CDCA7-HELLS is the sole nucleosome remodeling complex whose deficiency abrogates the maintenance of DNA methylation. We here identify the unique zinc-finger domain of CDCA7 as an evolutionarily conserved hemimethylation-sensing zinc finger (HMZF) domain. Cryo-electron microscopy structural analysis of the CDCA7-nucleosome complex reveals that the HMZF domain can recognize hemimethylated CpG in the outward-facing DNA major groove within the nucleosome core particle, whereas UHRF1, the critical activator of the maintenance methyltransferase DNMT1, cannot. CDCA7 recruits HELLS to hemimethylated chromatin and facilitates UHRF1-mediated H3 ubiquitylation associated with replication-uncoupled maintenance DNA methylation. We propose that the CDCA7-HELLS nucleosome remodeling complex assists the maintenance of DNA methylation on chromatin by sensing hemimethylated CpG that is otherwise inaccessible to UHRF1 and DNMT1. PubMed: 39178260DOI: 10.1126/sciadv.adp5753 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3 Å) |
Structure validation
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