Stereochemistry-dependent bending in oligonucleotide duplexes induced by site-specific covalent benzo[a]pyrene diol epoxide-guanine lesions

Rong Xu, Bing Mao, Jing Xu, Bin Li, Sheryl Birke, Charles E. Swenberg, Nicholas Geacintov

Research output: Contribution to journalArticle

Abstract

The apparent persistence length of enzymatically linearized plBI30 plasmid DNA molecules ̃2300 bp long, as measured by a hydrodynamic linear flow dlchroism method, Is markedly decreased after covalent binding of the highly tumorigenic benzo[a]pyrene metabolite 7R,8S-dlhydroxy-9S, 10R-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(+)-anti-BPDE]. In striking contrast, the binding of the non-tumorigenlc, mirror-image 7S,8R,9R,10S enantiomer [(-)-anfi-BPDE] to DNA has no measurable effect on Its alignment in hydrodynamic flow gradients (≤22.2% of the DNA bases modified). In order to relate this effect to BPDE-nucleotide lesions of defined stereochemistry, the bending induced by site-specifically placed and stereochemlcally defined (+)- and (-)-anti-BPDE-N2-dG lesions in an 11mer deoxyoligonucleotide duplex was studied by ligation and gel electrophoresls methods. Out of the four stereochemically isomerlc anti-BPDE-N2-deoxyguanosyl (dG) adducts with either (+)-trans, (-)-trans, (+)-cls, and (-)-cls adduct stereochemistry, only the (+ytrans adduct gives rise to prominent bends or flexible hinge joints In the modified oligonucleotide duplexes. Since both antf-BPDE enantlomers are known to bind preferentially to dG (≤85%), these observations can account for the differences in persistence lengths of DNA modified with either (+)-anti-BPDE or the chiral (-)-anti-BPDE isomer.

Original languageEnglish (US)
Pages (from-to)2314-2319
Number of pages6
JournalNucleic Acids Research
Volume23
Issue number12
DOIs
StatePublished - Jun 25 1995

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7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide
Stereochemistry
Oligonucleotides
Benzo(a)pyrene
Epoxy Compounds
Pyrene
Guanine
Persistence
Hydrodynamics
DNA
Gradient Flow
Dependent
Epoxy
Mirror
Alignment
Molecules
Enantiomers
Hinges
Nucleotides
Metabolites

ASJC Scopus subject areas

  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Health, Toxicology and Mutagenesis
  • Toxicology
  • Genetics(clinical)
  • Genetics

Cite this

Stereochemistry-dependent bending in oligonucleotide duplexes induced by site-specific covalent benzo[a]pyrene diol epoxide-guanine lesions. / Xu, Rong; Mao, Bing; Xu, Jing; Li, Bin; Birke, Sheryl; Swenberg, Charles E.; Geacintov, Nicholas.

In: Nucleic Acids Research, Vol. 23, No. 12, 25.06.1995, p. 2314-2319.

Research output: Contribution to journalArticle

Xu, Rong ; Mao, Bing ; Xu, Jing ; Li, Bin ; Birke, Sheryl ; Swenberg, Charles E. ; Geacintov, Nicholas. / Stereochemistry-dependent bending in oligonucleotide duplexes induced by site-specific covalent benzo[a]pyrene diol epoxide-guanine lesions. In: Nucleic Acids Research. 1995 ; Vol. 23, No. 12. pp. 2314-2319.
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AB - The apparent persistence length of enzymatically linearized plBI30 plasmid DNA molecules ̃2300 bp long, as measured by a hydrodynamic linear flow dlchroism method, Is markedly decreased after covalent binding of the highly tumorigenic benzo[a]pyrene metabolite 7R,8S-dlhydroxy-9S, 10R-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(+)-anti-BPDE]. In striking contrast, the binding of the non-tumorigenlc, mirror-image 7S,8R,9R,10S enantiomer [(-)-anfi-BPDE] to DNA has no measurable effect on Its alignment in hydrodynamic flow gradients (≤22.2% of the DNA bases modified). In order to relate this effect to BPDE-nucleotide lesions of defined stereochemistry, the bending induced by site-specifically placed and stereochemlcally defined (+)- and (-)-anti-BPDE-N2-dG lesions in an 11mer deoxyoligonucleotide duplex was studied by ligation and gel electrophoresls methods. Out of the four stereochemically isomerlc anti-BPDE-N2-deoxyguanosyl (dG) adducts with either (+)-trans, (-)-trans, (+)-cls, and (-)-cls adduct stereochemistry, only the (+ytrans adduct gives rise to prominent bends or flexible hinge joints In the modified oligonucleotide duplexes. Since both antf-BPDE enantlomers are known to bind preferentially to dG (≤85%), these observations can account for the differences in persistence lengths of DNA modified with either (+)-anti-BPDE or the chiral (-)-anti-BPDE isomer.

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