Targeting DNA Secondary Structures

Randy   M.   Wadkins

doi:10.2174/0929867003375461

Abstract

DNA secondary structures containing regions of single-stranded DNA have now been identified in the genomic DNA of a number of prokaryotic and eukaryotic species, including humans. Many of these secondary structures are associated with regions of DNA involved in regulation of transcription: promoters or upstream elements. The secondary structures involved appear likely to be hairpin or cruciform structures that may be recognition sites for binding of transcription factors. In the case of the coliphage N4 virion RNA polymerase, a defined hairpin in the polymerase promoter necessary for binding of the polymerase and regulation of transcription has been shown to be extruded under physiological conditions in plasmid DNA. The presence of single-stranded DNA in the promoters of several species suggests that regulatory hairpins may be involved in transcription of a number of genes. In support of this, hairpin- or cruciform-binding proteins have been identified from several species. These results imply that secondary structures in regulatory regions may be targets for drugs that bind and either block or enhance binding of proteins involved in transcription. In this review, we discuss the evidence for DNA secondary structures, particularly hairpins and cruciforms, in genomic DNA and review the studies to date of development of small molecules that can selectively bind these structures.

Keywords: DNA Secondary Structures, Prokaryotic, eukartyotic species, hairpin, cruciform structures, trancription factors, recognition sites, coliphage N4 virion RNA polymerase, cruciformn binding proteins, genomic DNA, Drosophila, single stranded DNA, ssDNA, transcription regulation, biological systems, malaria parasite P falciparum, N4 virion RNA polymerase vRNAP, E coli, bacteriophage N4, E coli DNA gyrase, nuclear factor I NFI, TFIIIA, dsDNA, xenopus kidney cell, actinomycin D, rRNA promoter, telomeres, telomerase, oxytricha nova tolemere binding protein, HIV 1 nucleocapsid protein NC, zinc finger protein, duplex DNA dGGAATTCC2, hairpin interactive agents, HIV1 reverse transcripase activity