2013
DOI: 10.1002/em.21806
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Sequence context modulation of polycyclic aromatic hydrocarbon‐induced mutagenesis

Abstract: DNA structural perturbations that are induced by site specifically and stereospecifically defined benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE) adducts are directly correlated with mutagenesis, leading to cellular transformation. Although previous investigations had established that replication of DNAs containing N6-BPDE dA adducts at the second position in the N-ras codon 61(CAA) (612) resulted exclusively in A to G transitions, NMR analyses not only established the structural basis for this transition m… Show more

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Cited by 3 publications
(2 citation statements)
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“…Nucleotide excision repair susceptibility of the (+)- trans-anti -[BP]- N 2 -dG adduct in several sequences shows that dynamic periodic denaturation of Watson–Crick base pairing on the 5′ flank of the lesion provides a strong recognition signal for repair in these sequences. , Biophysical studies showing marked local thermodynamic destabilization are consistent with this notion. Mutagenesis of the (+)- trans-anti -[BP]- N 2 -dG adduct also is context dependent. , Mutagenesis of the oxidative DNA damages 8-OxoG and Fapy·dG in human cells is also strongly dependent on DNA sequence context. , However, these and similar studies with other DNA lesions have been carried out in a limited number of DNA sequences. , Even so, a combination of structural (NMR and crystal structure analyses) and computation studies carried out by Geacintov, Patel, Stone, Broyde, Wetmore and others has provided much needed links between the structure and conformation of a lesion in different sequences and the biological effects of that lesion. ,,, …”
Section: Site-specific Lesion-derived Mutagenesismentioning
confidence: 99%
“…Nucleotide excision repair susceptibility of the (+)- trans-anti -[BP]- N 2 -dG adduct in several sequences shows that dynamic periodic denaturation of Watson–Crick base pairing on the 5′ flank of the lesion provides a strong recognition signal for repair in these sequences. , Biophysical studies showing marked local thermodynamic destabilization are consistent with this notion. Mutagenesis of the (+)- trans-anti -[BP]- N 2 -dG adduct also is context dependent. , Mutagenesis of the oxidative DNA damages 8-OxoG and Fapy·dG in human cells is also strongly dependent on DNA sequence context. , However, these and similar studies with other DNA lesions have been carried out in a limited number of DNA sequences. , Even so, a combination of structural (NMR and crystal structure analyses) and computation studies carried out by Geacintov, Patel, Stone, Broyde, Wetmore and others has provided much needed links between the structure and conformation of a lesion in different sequences and the biological effects of that lesion. ,,, …”
Section: Site-specific Lesion-derived Mutagenesismentioning
confidence: 99%
“…A prevalent mutation resulting from BaP exposure is a G to T transversion, a common mutation found in BaP-treated mammalian cells and the p53 gene of lung cancers of smokers [ 55 , 56 ]. The local sequence context of BaP-induced DNA damage also plays a role in the resulting mutation pattern [ 65 , 66 , 67 , 68 ].…”
Section: Selection and Switching Of Specialized Dna Polymerasesmentioning
confidence: 99%