DNA conformation selective intercalation of pluramycins into TBP-TATA box complex

Soung Joo Lee, Laurence H. Hurley

Research output: Contribution to journalArticle

Abstract

TDP (TATA binding protein), the primary transcription factor tliat recruits subsequent transcription machinery, binds io the TATA box through the extensive minor groove contacts and locally bends ihe DNA. This protein-induced distortion transiently creates an unv-ound site on the downstream side of the TATA box. and is favorably seized by piuramyrins, a group of novel threading intercalating arititumor antibiotics. To understand the detail of the dynamics of Ihe TATA box upon TBP binding, we have investigated the TUP-1 ATA box complexes using D Nase I arid piuramyrins. D Nase I foot print ing ex periinpnts revealed overdigested pattern rather than protection on both the if half A tract of the TATA box and the downstream flanking sequences at low i oncen t rations of protein, implying the unusual déformai ion of t he minor groove. A downstream ba.se-pair step in the protein-DNA complex showed the enhanced modification by a.11 pluramycins. However, pluramycins that have distinct, sugar substituants alkylated different guanines in the same base-pair step (CG : GC), indicating t hat the sugar substituents modulated orientations of ihe drugs. Taken together, it is proposed that the asymmetric recognition of the TBP-TATA complex originates trom the preferred distortion on the 3′ half A tract of the TATA box and that the propagated distortion results in the un winding of the specific downstream base-pair step. Those results also suggest the potential of pluramycins as molecular probes that detect uniquely deformed DNA duplexes through the specifii positioning of sugar substituents.

Original languageEnglish (US)
Pages (from-to)A1324
JournalFASEB Journal
Volume11
Issue number9
StatePublished - Dec 1 1997
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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