DNA tetraplex formation in the control region of c-myc
DNA tetraplex formation in the control region of c-myc
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DOI：
10.1093/nar/26.5.1167
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发表时间：
1998-03-01
影响因子：
14.9
通讯作者：
Kubista, M
中科院分区：
文献类型：
--
作者：
Simonsson, T;Pecinka, P;Kubista, M
c-myc癌基因是人类癌症中最常见的功能失调基因之一，是抗基因治疗的一个有吸引力的靶点。虽然人工合成的寡核苷酸通过其主要控制元件之一来沉默c-myc的表达，但它们的作用模式在体外很好地发挥作用，这里我们发现目标控制元件采用链内折叠DNA四联体，这需要钾离子来维持体外稳定性。我们认为四联体的形成对体内c-myc的激活很重要，并提出了一种转录起始机制，解释了抗基因治疗如何在分子水平上沉默c-myc。
The c-myc oncogene is one of the most commonly malfunctioning genes in human cancers, and is an attractive target for anti-gene therapy. Although synthetic oligonucleotides designed to silence c-myc expression via one of its major control elements function well in vitro, their mode of action has been indefinite, Here we show that the targeted control element adopts an intrastrand fold-back DNA tetraplex, which requires potassium ions for stability in vitro. We believe formation of the tetraplex is important for c-myc activation in vivo, and propose a transcription initiation mechanism that explains how anti-gene therapy silence c-myc at the molecular level.