ArticleBiochemistry2012
Nucleotide excision repair efficiencies of bulky carcinogen-DNA adducts are governed by a balance between stabilizing and destabilizing interactions.
Article in Biochemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 54 citations in OpenAlex.
- 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
- Utilizing biological experimental data and molecular dynamics for the classification of mutational hotspots through machine learning.Bioinformatics advances · 2024Article
- Impact of DNA sequences on DNA 'opening' by the Rad4/XPC nucleotide excision repair complex.DNA repair · 2021Article
- Carcinogen-induced DNA structural distortion differences in the RAS gene isoforms; the importance of local sequence.BMC chemistry · 2021Article
- Cellular levels and molecular dynamics simulations of estragole DNA adducts point at inefficient repair resulting from limited distortion of the double-stranded DNA helix.Archives of toxicology · 2020Article
- Lesion Sensing during Initial Binding by Yeast XPC/Rad4: Toward Predicting Resistance to Nucleotide Excision Repair.Chemical research in toxicology · 2018Article
- Impact of DNA lesion repair, replication and formation on the mutational spectra of environmental carcinogens: Aflatoxin BDNA repair · 2018Review
- Enhanced spontaneous DNA twisting/bending fluctuations unveiled by fluorescence lifetime distributions promote mismatch recognition by the Rad4 nucleotide excision repair complex.Nucleic acids research · 2018Article
- Repair-Resistant DNA Lesions.Chemical research in toxicology · 2017Review
- Nucleotide Excision Repair Lesion-Recognition Protein Rad4 Captures a Pre-Flipped Partner Base in a Benzo[a]pyrene-Derived DNA Lesion: How Structure Impacts the Binding Pathway.Chemical research in toxicology · 2017Article
- Poor response to platinum-based chemotherapy is associated with KRAS mutation and concomitant low expression of BRAC1 and TYMS in NSCLC.The Journal of international medical research · 2016Article
- Nucleotide Excision Repair and Transcription-coupled DNA Repair Abrogate the Impact of DNA Damage on Transcription.The Journal of biological chemistry · 2016Article
- Effect of base sequence context on the conformational heterogeneity of aristolactam-I adducted DNA: structural and energetic insights into sequence-dependent repair and mutagenicity.Toxicology research · 2016Article
- Base damage, local sequence context and TP53 mutation hotspots: a molecular dynamics study of benzo[a]pyrene induced DNA distortion and mutability.Nucleic acids research · 2015Article
- Adenine versus guanine DNA adducts of aristolochic acids: role of the carcinogen-purine linkage in the differential global genomic repair propensity.Nucleic acids research · 2015Article
- Recognition of Damaged DNA for Nucleotide Excision Repair: A Correlated Motion Mechanism with a Mismatched cis-syn Thymine Dimer Lesion.Biochemistry · 2015Article
- DNA Sequence Modulates Geometrical Isomerism of the trans-8,9- Dihydro-8-(2,6-diamino-4-oxo-3,4-dihydropyrimid-5-yl-formamido)- 9-hydroxy Aflatoxin B1 Adduct.Chemical research in toxicology · 2015Article
- ERCC1 and BRCA1 mRNA expressions are associated with clinical outcome of non-small cell lung cancer treated with platinum-based chemotherapy.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Article
- Structural basis for the recognition of diastereomeric 5',8-cyclo-2'-deoxypurine lesions by the human nucleotide excision repair system.Nucleic acids research · 2014Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The nucleotide excision repair (NER) machinery, the primary defense against cancer-causing bulky DNA lesions, is surprisingly inefficient in recognizing certain mutagenic DNA adducts and other forms of DNA damage. However, the biochemical basis of resistance to repair remains poorly understood. To address this problem, we have investigated a series of intercalated DNA-adenine lesions derived from carcinogenic polycyclic aromatic hydrocarbon (PAH) diol epoxide metabolites that differ in their response to the mammalian NER apparatus. These stereoisomeric PAH-derived adenine lesions represent ideal model systems for elucidating the effects of structural, dynamic, and thermodynamic properties that determine the recognition of these bulky DNA lesions by NER factors. The objective of this work was to gain a systematic understanding of the relation between aromatic ring topology and adduct stereochemistry with existing experimental NER efficiencies and known thermodynamic stabilities of the damaged DNA duplexes. For this purpose, we performed 100 ns molecular dynamics studies of the lesions embedded in identical double-stranded 11-mer sequences. Our studies show that, depending on topology and stereochemistry, stabilizing PAH-DNA base van der Waals stacking interactions can compensate for destabilizing distortions caused by these lesions that can, in turn, cause resistance to NER. The results suggest that the balance between helix stabilizing and destabilizing interactions between the adduct and nearby DNA residues can account for the variability of NER efficiencies observed in this class of PAH-DNA lesions.
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