Specific targeting of protein-DNA complexes by DNA-reactive drugs (+)- CC-1065 and pluramycins

Douglas Henderson, Laurence Hurley

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

To gain insight into the interactions between transcriptional factor proteins and DNA, the DNA-reactive drugs (+)-CC-1065 and pluramycin were used to target specific protein-DNA complexes. The structural features of the complex between the transcriptional activator Sp1 and the 21-base-pair repeat of the early promoter region of SV40 DNA were examined using hydroxyl-radical footprinting; (+)-CC-1065, a sequence-specific minor groove bending probe; and circularization experiments. The results show that the 21-base-pair repeat region has an intrinsically in-phase bent structure that is stabilized upon saturation Sp1 binding by protein-DNA and protein-protein interactions to produce a looping structure. The intercalating drug pluramycin was used to probe the structural details of the interaction between the TATA binding protein (TBP) and the TATA box DNA sequence. TBP, which directs initiation of RNA transcription, exhibits two-fold symmetry and apparently interacts with the TATA box in a symmetrical fashion. However, the interaction results in an asymmetric effect, in that transcription is initiated only in the downstream direction. Using pluramycin as a probe, it was determined that TBP binding to the human myoglobin TATA sequences enhances pluramycin reactivity at a site immediately downstream of the TATA box. The implications on transcriptional control of ternary complexes comprised of transcriptional factors, DNA, and DNA-reactive compounds will be presented.

Original languageEnglish (US)
Pages (from-to)75-87
Number of pages13
JournalJournal of Molecular Recognition
Volume9
Issue number2
DOIs
StatePublished - Mar 1996
Externally publishedYes

Fingerprint

CC 1065
Protein Transport
DNA
TATA-Box Binding Protein
Proteins
TATA Box
Pharmaceutical Preparations
Transcription
Base Pairing
Myoglobin
DNA sequences
DNA-Binding Proteins
Genetic Promoter Regions
Protein Binding
Hydroxyl Radical
pluramycin
RNA

Keywords

  • (+)-CC-1065
  • minor groove DNA binding
  • pluramycin
  • TATA box
  • TBP

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Computer Vision and Pattern Recognition
  • Immunology
  • Molecular Biology

Cite this

Specific targeting of protein-DNA complexes by DNA-reactive drugs (+)- CC-1065 and pluramycins. / Henderson, Douglas; Hurley, Laurence.

In: Journal of Molecular Recognition, Vol. 9, No. 2, 03.1996, p. 75-87.

Research output: Contribution to journalArticle

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