Occurrence of DNA sequences specifically recognized by drugs in human promoters.
Several DNA-binding drugs are being developed to create tailored molecules which can discriminate among the different sequences of the whole genome. By discriminating among specific sites in DNA, these molecules may provide optimal drug therapy. The complete sequencing of the human genome offers a wealth of DNA targets to be analyzed as potential drug-binding sites. To increase our understanding of DNA-drug interactions and their selectivity, we have studied the relative and absolute occurrence of CG-rich sequences, of various lengths, in human gene promoters. In several promoters, including those of oncogenes, cell cycle regulation factors, tumor suppressors and housekeeping genes, the presence of potential binding sites containing CpG steps (in which many drugs are known to intercalate) is variable, but in many cases these sites are not randomly distributed. Sequences 6-7 base pairs in length, like CGCCCG or CGCCCCG, occur only once in some promoters, thus they may be potentially specific therapeutic targets.
Mansilla
Sylvia
S
Departamento de Biología Molecular y Celular, Instituto de Biología Molecular de Barcelona, CSIC, Jordi Girona, 18-26, 08034 Barcelona, Spain. jpmbmc@cid.csic.es
Portugal
José
J
D024682:BRCA2 Protein / Q000235:genetics; D001483:Base Sequence; D001665:Binding Sites; D019938:Cyclin D1 / Q000235:genetics; D004247:DNA / Q000737:chemistry* / Q000235:genetics*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011401:Promoter Regions, Genetic
D024682:BRCA2 Protein; D004364:Pharmaceutical Preparations; D019938:Cyclin D1; D004247:DNA; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases