ArticleNucleic acids research2009
Influence of local sequence context on damaged base conformation in human DNA polymerase iota: molecular dynamics studies of nucleotide incorporation opposite a benzo[a]pyrene-derived adenine lesion.
Article in Nucleic acids research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 18 citations in OpenAlex.
- Assessing the contribution of rare DNA states to cancer mutational signatures using sequence-specific conformational fingerprinting.Nature communications · 2026Article
- Assessing the contribution of rare DNA states to cancer mutational signatures using sequence-specific conformational fingerprinting.Research square · 2025Article
- Utilizing biological experimental data and molecular dynamics for the classification of mutational hotspots through machine learning.Bioinformatics advances · 2024Article
- Carcinogen-induced DNA structural distortion differences in the RAS gene isoforms; the importance of local sequence.BMC chemistry · 2021Article
- Structure and function relationships in mammalian DNA polymerases.Cellular and molecular life sciences : CMLS · 2020Review
- Review
- Genome maintenance and bioenergetics of the long-lived hypoxia-tolerant and cancer-resistant blind mole rat, Spalax: a cross-species analysis of brain transcriptome.Scientific reports · 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
- Structural and energetic characterization of the major DNA adduct formed from the food mutagen ochratoxin A in the NarI hotspot sequence: influence of adduct ionization on the conformational preferences and implications for the NER propensity.Nucleic acids research · 2014Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Human DNA polymerase iota is a lesion bypass polymerase of the Y family, capable of incorporating nucleotides opposite a variety of lesions in both near error-free and error-prone bypass. With undamaged templating purines polymerase iota normally favors Hoogsteen base pairing. Polymerase iota can incorporate nucleotides opposite a benzo[a]pyrene-derived adenine lesion (dA*); while mainly error-free, the identity of misincorporated bases is influenced by local sequence context. We performed molecular modeling and molecular dynamics simulations to elucidate the structural basis for lesion bypass. Our results suggest that hydrogen bonds between the benzo[a]pyrenyl moiety and nearby bases limit the movement of the templating base to maintain the anti glycosidic bond conformation in the binary complex in a 5'-CAGA*TT-3' sequence. This facilitates correct incorporation of dT via a Watson-Crick pair. In a 5'-TTTA*GA-3' sequence the lesion does not form these hydrogen bonds, permitting dA* to rotate around the glycosidic bond to syn and incorporate dT via a Hoogsteen pair. With syn dA*, there is also an opportunity for increased misincorporation of dGTP. These results expand our understanding of the versatility and flexibility of polymerase iota and its lesion bypass functions in humans.
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