Polyamines preferentially interact with bent adenine tracts in double-stranded DNA

TY - JOUR

T1 - Polyamines preferentially interact with bent adenine tracts in double-stranded DNA

AU - Lindemose, Søren

AU - Møllegaard, Niels Erik

AU - Nielsen, Peter E.

PY - 2005

Y1 - 2005

N2 - 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.

AB - 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.

KW - Adenine/metabolism

KW - Binding Sites

KW - DNA/chemistry

KW - Humans

KW - Nucleic Acid Conformation

KW - Polyamines/metabolism

KW - Promoter Regions, Genetic

KW - Uranyl Nitrate/chemistry

U2 - 10.1093/nar/gki319

DO - 10.1093/nar/gki319

M3 - Journal article

C2 - 15788751

SN - 0305-1048

VL - 33

SP - 1790

EP - 1803

JO - Nucleic Acids Research

JF - Nucleic Acids Research

IS - 6

ER -