ArticleNucleic acids research2019
Structure and mechanism of pyrimidine-pyrimidone (6-4) photoproduct recognition by the Rad4/XPC nucleotide excision repair complex.
Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 67 citations in OpenAlex.
- DGCR8 regulates multiple processes of transcription coupled nucleotide excision repair.Scientific reports · 2026Article
- Dynamic Assemblies in Genome Maintenance.Advances in experimental medicine and biology · 2026Review
- Review
- UV-induced reorganization of 3D genome mediates DNA damage response.Nature communications · 2025Article
- Evidence for intrinsic DNA dynamics and deformability in damage sensing by the Rad4/XPC nucleotide excision repair complex.Nucleic acids research · 2025Article
- Relative genotoxicity of polycyclic aromatic hydrocarbons inferred from free energy perturbation approaches.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- ASH1L guards cis-regulatory elements against cyclobutane pyrimidine dimer induction.Nucleic acids research · 2024Article
- Interplay of the Tfb1 pleckstrin homology domain with Rad2 and Rad4 in transcription coupled and global genomic nucleotide excision repair.Nucleic acids research · 2024Article
- Ultraviolet Radiation Biological and Medical Implications.Current issues in molecular biology · 2024Review
- A novel replication initiation region encoded in a widespread Acinetobacter plasmid lineage carrying a blaNDM-1 gene.PloS one · 2024Article
- Differing structures and dynamics of two photolesions portray verification differences by the human XPD helicase.Nucleic acids research · 2023Article
- Detection of oxaliplatin- and cisplatin-DNA lesions requires different global genome repair mechanisms that affect their clinical efficacy.NAR cancer · 2023Article
- Mapping the recognition pathway of cyclobutane pyrimidine dimer in DNA by Rad4/XPC.Nucleic acids research · 2023Article
- Recovery of protein synthesis to assay DNA repair activity in transcribed genes in living cells and tissues.Nucleic acids research · 2023Article
- Aging, Physical Exercise, Telomeres, and Sarcopenia: A Narrative Review.Biomedicines · 2023Review
- Structural modeling and analyses of genetic variations in the human XPC nucleotide excision repair protein.Journal of biomolecular structure & dynamics · 2023Article
- A nuclease-mimetic platinum nanozyme induces concurrent DNA platination and oxidative cleavage to overcome cancer drug resistance.Nature communications · 2022Article
- The XPA Protein-Life under Precise Control.Cells · 2022Review
- "Flexible hinge" dynamics in mismatched DNA revealed by fluorescence correlation spectroscopy.Journal of biological physics · 2022Article
- Nucleotide excision repair: a versatile and smart toolkit.Acta biochimica et biophysica Sinica · 2022Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
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.
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