Genome integrity is essential for proper cell function such that genetic instability can result in cellular dysfunction and disease. Mutations in the human genome are not random, and occur more frequently at "hotspot" regions that often co-localize with sequences that have the capacity to adopt alternative (i.e. non-B) DNA structures. Non-B DNA-forming sequences are mutagenic, can stimulate the formation of DNA double-strand breaks, and are highly enriched at mutation hotspots in human cancer genomes. Thus, small molecules that can modulate the conformations of these structure-forming sequences may prove beneficial in the prevention and/or treatment of genetic diseases. Further, the development of molecular probes to interrogate the roles of non-B DNA structures in modulating DNA function, such as genetic instability in cancer etiology are warranted. Here, we discuss reported non-B DNA stabilizers, destabilizers, and probes, recent assays to identify ligands, and the potential biological applications of these DNA structure-modulating molecules.

中文翻译：

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使用小分子调节 DNA 结构形成。


基因组完整性对于正常的细胞功能至关重要，遗传不稳定性可能导致细胞功能障碍和疾病。人类基因组中的突变不是随机的，并且更频繁地发生在“热点”区域，这些区域通常与能够采用替代（即非 B）DNA 结构的序列共定位。非 B DNA 形成序列具有诱变性，可以刺激 DNA 双链断裂的形成，并且在人类癌症基因组的突变热点处高度富集。因此，可以调节这些结构形成序列的构象的小分子可能被证明有益于预防和/或治疗遗传疾病。此外，有必要开发分子探针来探究非 B DNA 结构在调节 DNA 功能中的作用，例如癌症病因学中的遗传不稳定性。在这里，我们讨论已报道的非 B DNA 稳定剂、去稳定剂和探针、最近鉴定配体的测定方法，以及这些 DNA 结构调节分子的潜在生物学应用。