8TLK

CDCA7 (Human) Binds Non-B-form 32-mer DNA oligo Containing a 5mC

Summary for 8TLK

• Entry DOI: 10.2210/pdb8tlk/pdb
• Descriptor: Cell division cycle-associated protein 7, DNA (32-MER), ZINC ION, ... (7 entities in total)
• Functional Keywords: protein-dna complex, dna binding protein, zinc fingers, chromatin architecture, dna binding protein-dna complex, dna binding protein/dna
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 53291.16

Authors

Horton, J.R.,Ren, R.,Cheng, X. (deposition date: 2023-07-26, release date: 2024-08-21, Last modification date: 2024-08-28)

Primary citation

Hardikar, S.,Ren, R.,Ying, Z.,Horton, J.R.,Bramble, M.D.,Liu, B.,Lu, Y.,Liu, B.,Dan, J.,Zhang, X.,Cheng, X.,Chen, T.
The ICF syndrome protein CDCA7 harbors a unique DNA-binding domain that recognizes a CpG dyad in the context of a non-B DNA.
Biorxiv, 2023

PubMed Abstract: , encoding a protein with a C-terminal cysteine-rich domain (CRD), is mutated in immunodeficiency, centromeric instability and facial anomalies (ICF) syndrome, a disease related to hypomethylation of juxtacentromeric satellite DNA. How CDCA7 directs DNA methylation to juxtacentromeric regions is unknown. Here, we show that the CDCA7 CRD adopts a unique zinc-binding structure that recognizes a CpG dyad in a non-B DNA formed by two sequence motifs. CDCA7, but not ICF mutants, preferentially binds the non-B DNA with strand-specific CpG hemi-methylation. The unmethylated sequence motif is highly enriched at centromeres of human chromosomes, whereas the methylated motif is distributed throughout the genome. At S phase, CDCA7, but not ICF mutants, is concentrated in constitutive heterochromatin foci, and the formation of such foci can be inhibited by exogenous hemi-methylated non-B DNA bound by the CRD. Binding of the non-B DNA formed in juxtacentromeric regions during DNA replication provides a mechanism by which CDCA7 controls the specificity of DNA methylation.

PubMed: 38168392
DOI: 10.1101/2023.12.15.571946

Experimental method

X-RAY DIFFRACTION (2.99 Å)