9UZ7

Cryo-EM structure of the nucleosome core particle with site-specific DNA-histone crosslinking

Summary for 9UZ7

• Entry DOI: 10.2210/pdb9uz7/pdb
• EMDB information: 64640
• Descriptor: Histone H3.1, Histone H4, Histone H2A type 1-B/E, ... (7 entities in total)
• Functional Keywords: histone, nucleosome, dna binding protein, dna binding protein-dna complex, dna binding protein/dna
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 10
• Total formula weight: 198268.95

Authors

Zhou, C.Z.,Li, H.T.,Shan, X.J.,Ji, G.Y. (deposition date: 2025-05-16, release date: 2026-05-06, Last modification date: 2026-05-27)

Primary citation

Shan, X.,Ji, G.,Li, J.,Ren, M.,Ma, J.,Zhou, Y.,Li, H.,Zhou, C.
DNA-histone cross-link locks the nucleosome structure and disrupts its recognition and processing.
Protein Cell, 17:476-482, 2026

PubMed Abstract: DNA-histone cross-links (DHCs) frequently arise within nucleosomes during DNA damage and repair processes. However, the functional consequences of DHC within nucleosomes remain largely unexplored. In this study, we prepared structurally homogeneous nucleosomes containing a single, site-specific DHC using click chemistry and systematically evaluated the impact of DHC on nucleosome structure and function. Our results show that DHC markedly enhances nucleosome thermal stability and completely blocks both thermally induced passive sliding and chromatin remodeler-mediated active sliding. Moreover, DHC obstructs SP6 RNA polymerase-driven transcription elongation through nucleosomes, leading to premature termination approximately 15 bp upstream of the cross-linking site. DHC also increases histone resistance to proteolytic digestion within nucleosomes. These findings suggest that even a single DHC can substantially lock and rigidify the nucleosome structure and broadly interfere with the recognition and processing of nucleosomes by various cellular machineries, thereby rendering DHC a highly toxic and persistent form of DNA damage. This in vitro study highlights the unique impact of DHC on nucleosome architecture and is expected to motivate further exploration of its biological roles in vivo.

PubMed: 41206067
DOI: 10.1093/procel/pwaf094

Experimental method

ELECTRON MICROSCOPY (3.24 Å)