Lindemose Søren, Nielsen Peter E, Møllegaard Niels Erik
Department of Medical Biochemistry and Genetics, The Panum Institute, University of Copenhagen Blegdamsvej 3C, 2200 Copenhagen N, Denmark.
Nucleic Acids Res. 2005 Mar 23;33(6):1790-803. doi: 10.1093/nar/gki319. Print 2005.
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.
多胺,如腐胺、亚精胺和精胺,与基因表达的调控存在间接关联,并且它们在癌细胞中的浓度通常会升高。尽管已证明多胺对转录因子与同源DNA靶点的结合有影响,但对多胺生物作用的机制却知之甚少。我们现在利用铀酰光探测法证明,亚毫摩尔浓度的多胺优先结合双链DNA中的弯曲腺嘌呤序列。这些结果首次明确证明了多胺与DNA的序列特异性结合,从而表明多胺在不同基因转录活性方面的细胞效应,至少部分可能是多胺在DNA序列水平上与启动子发生序列特异性相互作用的直接结果。