Stereochemistry-dependent bending in oligonucleotide duplexes induced by site-specific covalent benzo[a]pyrene diol epoxide-guanine lesions.
AUTOR(ES)
Xu, R
RESUMO
The apparent persistence length of enzymatically linearized pIBI30 plasmid DNA molecules approximately 2300 bp long, as measured by a hydrodynamic linear flow dichroism method, is markedly decreased after covalent binding of the highly tumorigenic benzo[a]pyrene metabolite 7R,8S-dihydroxy-9S,10R-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(+)-anti-BPDE]. In striking contrast, the binding of the non-tumorigenic, mirror-image 7S,8R,9R,10S enantiomer [(-)-anti-BPDE] to DNA has no measurable effect on its alignment in hydrodynamic flow gradients (< or = 2.2% 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 stereochemically defined (+)- and (-)-anti-BPDE-N2-dG lesions in an 11mer deoxyoligonucleotide duplex was studied by ligation and gel electrophoresis methods. Out of the four stereochemically isomeric anti-BPDE-N2-deoxyguanosyl (dG) adducts with either (+)-trans, (-)-trans, (+)-cis, and (-)-cis adduct stereochemistry, only the (+)-trans adduct gives rise to prominent bends or flexible hinge joints in the modified oligonucleotide duplexes. Since both anti-BPDE enantiomers are known to bind preferentially to dG (> or = 85%), these observations can account for the differences in persistence lengths of DNA modified with either (+)-anti-BPDE or the chiral (-)-anti-BPDE isomer.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=307023Documentos Relacionados
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