6CFI

Crystal structure of Rad4-Rad23 bound to a 6-4 photoproduct UV lesion

Summary for 6CFI

• Entry DOI: 10.2210/pdb6cfi/pdb
• Descriptor: DNA repair protein RAD4, UV excision repair protein RAD23, DNA('-D(*TP*TP*GP*AP*CP*TP*CP*AP*AP*CP*AP*TP*CP*CP*AP*AP*AP*GP*CP*TP*AP*CP*AP*A)-'), ... (4 entities in total)
• Functional Keywords: nucleotide excision repair, dna damage repair, xeroderma pigmentosum, ultraviolet, xpc, dna binding protein-dna complex, dna binding protein/dna
• Biological source: Saccharomyces cerevisiae S288c (Baker's yeast); More
• Total number of polymer chains: 4
• Total formula weight: 95120.48

Authors

Min, J.,Jeffrey, P.D. (deposition date: 2018-02-15, release date: 2019-02-27, Last modification date: 2024-03-13)

Primary citation

Paul, D.,Mu, H.,Zhao, H.,Ouerfelli, O.,Jeffrey, P.D.,Broyde, S.,Min, J.H.
Structure and mechanism of pyrimidine-pyrimidone (6-4) photoproduct recognition by the Rad4/XPC nucleotide excision repair complex.
Nucleic Acids Res., 47:6015-6028, 2019

PubMed Abstract: Failure in repairing ultraviolet radiation-induced DNA damage can lead to mutations and cancer. Among UV-lesions, the pyrimidine-pyrimidone (6-4) photoproduct (6-4PP) is removed from the genome much faster than the cyclobutane pyrimidine dimer (CPD), owing to the more efficient recognition of 6-4PP by XPC-RAD23B, a key initiator of global-genome nucleotide excision repair (NER). Here, we report a crystal structure of a Rad4-Rad23 (yeast XPC-Rad23B ortholog) bound to 6-4PP-containing DNA and 4-μs molecular dynamics (MD) simulations examining the initial binding of Rad4 to 6-4PP or CPD. This first structure of Rad4/XPC bound to a physiological substrate with matched DNA sequence shows that Rad4 flips out both 6-4PP-containing nucleotide pairs, forming an 'open' conformation. The MD trajectories detail how Rad4/XPC initiates 'opening' 6-4PP: Rad4 initially engages BHD2 to bend/untwist DNA from the minor groove, leading to unstacking and extrusion of the 6-4PP:AA nucleotide pairs towards the major groove. The 5' partner adenine first flips out and is captured by a BHD2/3 groove, while the 3' adenine extrudes episodically, facilitating ensuing insertion of the BHD3 β-hairpin to open DNA as in the crystal structure. However, CPD resists such Rad4-induced structural distortions. Untwisting/bending from the minor groove may be a common way to interrogate DNA in NER.

PubMed: 31106376
DOI: 10.1093/nar/gkz359

Experimental method

X-RAY DIFFRACTION (3.36241919841 Å)