一种新型小分子，可改变端粒保护蛋白复合体的完整性并在端粒处引发DNA损伤反应。
A novel small molecule that alters shelterin integrity and triggers a DNA-damage response at telomeres.
作者信息
Rodriguez Raphaël, Müller Sebastian, Yeoman Justin A, Trentesaux Chantal, Riou Jean-François, Balasubramanian Shankar
机构信息
The University Chemical Laboratory, Lensfield Road, Cambridge, CB2 1EW, UK.
出版信息
J Am Chem Soc. 2008 Nov 26;130(47):15758-9. doi: 10.1021/ja805615w.
Abstract
We describe a novel synthetic small molecule which shows an unprecedented stabilization of the human telomeric G-quadruplex with high selectivity relative to double-stranded DNA. We report that this compound can be used in vitro to inhibit telomerase activity and to uncap human POT1 (protection of telomeres 1) from the telomeric G-overhang. We also show that the small molecule G-quadruplex binder induces a partial alteration of shelterin through POT1 uncapping from telomeres in human HT1080 cancer cells and the presence of gammaH2AX foci colocalized at telomeres.
摘要
我们描述了一种新型合成小分子，它对人端粒G-四链体具有前所未有的稳定作用，相对于双链DNA具有高选择性。我们报告称，该化合物可在体外用于抑制端粒酶活性，并从端粒G-突出端解开人POT1（端粒保护蛋白1）。我们还表明，这种小分子G-四链体结合剂通过在人HT1080癌细胞中端粒的POT1解开以及端粒处共定位的γH2AX焦点的存在，诱导了端粒保护蛋白复合体的部分改变。
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