9LOX

Cryo-EM structure of the chromatin remodeler Rad26 bound to the nucleosome at SHL6

Summary for 9LOX

• Entry DOI: 10.2210/pdb9lox/pdb
• EMDB information: 63262
• Descriptor: Histone H3, Histone H4, Histone H2A, ... (7 entities in total)
• Functional Keywords: rad26, csb, ercc6, chromatin remodeler, dna repair, komagataella phaffii, komagataella pastoris, histone h2a, histone h2b, histone h3, histone h4, dna, epigenetic, gene regulation, cryo-em, dna binding protein
• Biological source: Komagataella phaffii; More
• Total number of polymer chains: 11
• Total formula weight: 342641.11

Authors

Fukushima, Y.,Takizawa, Y.,Kinoshita, C.,Ogasawara, M.,Kagawa, W.,Kurumizaka, H. (deposition date: 2025-01-23, release date: 2026-07-29, Last modification date: 2026-08-12)

Primary citation

Fukushima, Y.,Kinoshita, C.,Negishi, L.,Kujirai, T.,Kobayashi, Y.,Ogasawara, M.,Ehara, H.,Sekine, S.I.,Kagawa, W.,Kurumizaka, H.,Takizawa, Y.
Structural basis of nucleosome remodeling by Cockayne syndrome B homologue Komagataella phaffii Rad26.
Nat Commun, 17:-, 2026

PubMed Abstract: Rad26, a yeast homologue of mammalian Cockayne syndrome protein B (CSB), plays an essential role in transcription-coupled nucleotide excision repair (TC-NER). Rad26/CSB binds RNA polymerase II stalled at DNA lesions and recruits DNA repair factors, functioning as a molecular scaffold. In addition, Rad26/CSB possesses nucleosome-remodeling activity that may help restore transcription after DNA repair. Here we determine the cryo-electron microscopy structure of the Rad26/CSB-nucleosome complex. Rad26/CSB binds near the nucleosomal entry/exit region (superhelical location ±6) through a unique mechanism in which its ATPase domains, Lobe 1 and Lobe 2, engage nucleosomal DNA in a reverse orientation compared with other remodelers such as Snf2 and Ino80. Mutational, biochemical, and crosslinking mass-spectrometric analyses demonstrate the requirement of the KR loop for nucleosome binding and remodeling. Furthermore, we show that N-terminal auto-inhibition involves long-range contacts between the disordered N-terminus and the Lobe 2 region, and is relieved by mutations of Leu8 and Leu11. These findings reveal the structural basis of Rad26/CSB-mediated nucleosome remodeling in TC-NER.

PubMed: 42342665
DOI: 10.1038/s41467-026-73500-7

Experimental method

ELECTRON MICROSCOPY (3.5 Å)