Targeting DNA secondary structures.
Targeting DNA secondary structures.
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DOI：
10.2174/0929867003375461
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发表时间：
2000
影响因子：
4.1
通讯作者：
R. M. Wadkins
中科院分区：
文献类型：
--
作者：
R. M. Wadkins
包含单链DNA区域的DNA二级结构已经在许多原核生物和真核生物（包括人类）的基因组DNA中被鉴定出来。这些二级结构中的许多都与参与转录调控的DNA区域有关：启动子或上游元件。所涉及的二级结构可能是发夹或十字形结构，可能是转录因子结合的识别位点。在噬菌体N4病毒粒子RNA聚合酶的情况下，在聚合酶启动子中有一个明确的发夹，这是聚合酶结合和转录调节所必需的，已被证明在生理条件下在质粒DNA中被挤出。在一些物种的启动子中单链DNA的存在表明，调控发夹可能参与了许多基因的转录。为了支持这一点，已经从几个物种中鉴定出了发夹或十字形结合蛋白。这些结果表明，调控区域的二级结构可能是药物结合、阻断或增强参与转录的蛋白质结合的靶点。在这篇综述中，我们讨论了DNA二级结构的证据，特别是发夹和十字形，在基因组DNA中，并回顾了迄今为止的研究开发的小分子，可以选择性地结合这些结构。
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.