A model for the sequence-dependent DNA binding of 4',6-diamidino-2-phenylindole (DAPI).
A study on the sequence dependent DNA binding mode of DAPI has been carried out on pUC8 and the beta gal promoter region by restriction endonuclease and DNAase I protection experiments. A molecular model depicting drug interaction at the level of selected palyndromes has also been constructed that confirms the A-T sequence specificity of the compound. Experimental data indicate that the binding sites for RNA polymerase and cyclic AMP receptor protein (CRP) in the beta gal gene are privileged locales for DAPI interaction, a feature that explains impairment of transcription at this level. From a stereochemical view point, DAPI binding to DNA minor groove, while being incompatible with promoter unwinding in the open complex, may also disturb optimal contacts with proteins regulating RNA polymerase activity.
Parolin
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Institute of Microbiology, University of Padova, Italy.
Zanotti
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Palù
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D001482:Base Composition; D001483:Base Sequence; D001665:Binding Sites; D002352:Carrier Proteins; D002373:Cyclic AMP Receptor Protein / Q000378:metabolism; D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D004262:DNA Restriction Enzymes / Q000378:metabolism; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D003850:Deoxyribonuclease I; D007211:Indoles; D007364:Intercalating Agents; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D010957:Plasmids; D011401:Promoter Regions, Genetic; D013329:Structure-Activity Relationship; D001616:beta-Galactosidase / Q000235:genetics
D002352:Carrier Proteins; D002373:Cyclic AMP Receptor Protein; D007211:Indoles; D007364:Intercalating Agents; D009838:Oligodeoxyribonucleotides; C007293:DAPI; D004247:DNA; D012321:DNA-Directed RNA Polymerases; D004262:DNA Restriction Enzymes; D003850:Deoxyribonuclease I; D001616:beta-Galactosidase