Ulyanov N B, Bishop K D, Ivanov V I, James T L
Department of Pharmaceutical Chemistry, University of California, San Francisco 94143.
Nucleic Acids Res. 1994 Oct 11;22(20):4242-9. doi: 10.1093/nar/22.20.4242.
Short direct repeat sequences are often found in regulatory regions of various genes; in some cases they display hypersensitivity to S1 nuclease cleavage in supercoiled plasmids. A non-standard DNA structure (Slipped Loop Structure, or SLS) has been proposed for these regions in order to explain the S1 cleavage data; the formation of this structure may be involved in the regulation of transcription. The structure can be generally classified as a particular type of pseudoknot. To date, no detailed stereochemical model has been developed. We have applied one-dimensional 1H NMR spectroscopy to study a synthetic DNA, 55 nucleotides in length, which cannot fold as a standard hairpin but which may favor the SLS formation. AT base pairs were identified, consistent only with the formation of an additional, tertiary miniduplex in the SLS. An all-atom stereochemically sound model has been developed for the SLS with the use of conformational calculations. The model building studies have demonstrated that the tertiary miniduplex can be formed for one of the plausible SLS isomers, but not for the other.
短的直接重复序列经常出现在各种基因的调控区域；在某些情况下，它们对超螺旋质粒中的S1核酸酶切割表现出超敏性。为了解释S1切割数据，已针对这些区域提出了一种非标准DNA结构（滑环结构，或SLS）；这种结构的形成可能参与转录调控。该结构通常可归类为一种特殊类型的假结。迄今为止，尚未建立详细的立体化学模型。我们应用一维1H NMR光谱来研究一种合成DNA，其长度为55个核苷酸，它不能折叠成标准发夹结构，但可能有利于SLS的形成。已鉴定出AT碱基对，这仅与SLS中额外的三级小双链体的形成一致。通过构象计算，已为SLS建立了一个全原子立体化学合理的模型。模型构建研究表明，对于一种可能的SLS异构体可以形成三级小双链体，但对于另一种则不能。
