Polyamines preferentially interact with bent adenine tracts in double-stranded DNA.
Polyamines, such as putrescine, spermidine and spermine, have indirectly been linked with the regulation of gene expression, and their concentrations are typically increased in cancer cells. Although effects on transcription factor binding to cognate DNA targets have been demonstrated, the mechanisms of the biological action of polyamines is poorly understood. Employing uranyl photo-probing we now demonstrate that polyamines at submillimolar concentrations bind preferentially to bent adenine tracts in double-stranded DNA. These results provide the first clear evidence for the sequence-specific binding of polyamines to DNA, and thereby suggest a mechanism by which the cellular effects of polyamines in terms of differential gene transcriptional activity could, at least partly, be a direct consequence of sequence-specific interactions of polyamines with promoters at the DNA sequence level.
Lindemose
Søren
S
Department of Medical Biochemistry and Genetics, The Panum Institute, University of Copenhagen Blegdamsvej 3C, 2200 Copenhagen N, Denmark.
Nielsen
Peter E
PE
Møllegaard
Niels Erik
NE
D000225:Adenine / Q000378:metabolism*; D001665:Binding Sites; D004247:DNA / Q000737:chemistry* / Q000378:metabolism / Q000528:radiation effects; D006801:Humans; D009690:Nucleic Acid Conformation; D011073:Polyamines / Q000378:metabolism* / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D014502:Uranyl Nitrate / Q000737:chemistry
D011073:Polyamines; D014502:Uranyl Nitrate; D004247:DNA; D000225:Adenine