SNAP-annotated 5mC-DNA-protein interactions: PDB entry 8yv8

PDB-id

8yv8; DSSR-derived features in text and JSON formats; DNAproDB

Class

DNA binding protein

Method

cryo-EM (3.0 Å)

Summary

cryo-EM structure of cdca7 bound to nucleosome including hemimethylated cpg site in widom601 positioning sequence.

Reference

Wassing IE, 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 (2024): "CDCA7 is an evolutionarily conserved hemimethylated DNA sensor in eukaryotes." Sci Adv, 10, eadp5753. doi: 10.1126/sciadv.adp5753.

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.

• The contacts include paired nucleotides (mostly a G in Watson-Crick G-C pairing) and amino-acids within a 4.5-Å distance cutoff to base atoms of 5mC.
• The structure is oriented in the base reference frame of 5mC, allowing for easy comparison and direct superimposition between entries.
• The black sphere (•) denotes the 5-methyl carbon atom in 5mC.