肽核酸（PNA）与非模板DNA链的结合会干扰转录，这表明存在一种由R环形成介导的阻断机制。
PNA binding to the non-template DNA strand interferes with transcription, suggesting a blockage mechanism mediated by R-loop formation.
作者信息
Belotserkovskii Boris P, Hanawalt Philip C
机构信息
Department of Biology, Stanford University, Stanford, California.
出版信息
Mol Carcinog. 2015 Nov;54(11):1508-12. doi: 10.1002/mc.22209. Epub 2014 Aug 30.
Abstract
Peptide Nucleic Acids (PNAs) are artificial DNA mimics with superior nucleic acid binding capabilities. T7 RNA polymerase (T7 RNAP) transcription upon encountering PNA bound to the non-template DNA strand was studied in vitro. A characteristic pattern of blockage signals was observed, extending downstream from the PNA binding site, similar to that produced by G-rich homopurine-homopyrimidine (hPu-hPy) sequences and likely caused by R-loop formation. Since blocked transcription complexes in association with stable R-loops may interfere with replication and in some cases trigger apoptosis, targeted R-loop formation might be employed to inactivate selected cells, such as those in tumors, based upon their unique complement of expressed genes.
摘要
肽核酸（PNA）是具有卓越核酸结合能力的人工DNA模拟物。我们在体外研究了T7 RNA聚合酶（T7 RNAP）在遇到与非模板DNA链结合的PNA时的转录情况。观察到一种特征性的阻断信号模式，从PNA结合位点向下游延伸，类似于富含鸟嘌呤的同型嘌呤-同型嘧啶（hPu-hPy）序列产生的模式，可能是由R环形成引起的。由于与稳定R环相关的转录复合物阻断可能会干扰复制，在某些情况下还会引发细胞凋亡，基于肿瘤细胞等特定细胞所表达基因的独特互补性，靶向R环形成可用于使这些细胞失活。
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