POT1-TPP1 regulates telomeric overhang structural dynamics.
POT1-TPP1 regulates telomeric overhang structural dynamics.
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DOI：
10.1016/j.str.2012.08.018
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发表时间：
2012-11-07
期刊：
影响因子：
5.7
通讯作者：
Myong, Sua
中科院分区：
文献类型：
--
作者：
Hwang, Helen;Buncher, Noah;Opresko, Patricia L.;Myong, Sua
人类端粒具有TTAGGG重复的单链DNA（ssDNA）突出端，其可以自我折叠成G-四链体结构。POT 1特异性结合端粒突出端，并与TPP 1合作调节端粒延长和加帽，尽管其机制仍然难以捉摸。在这里，我们表明，POT 1稳定地结合到折叠的端粒G-四链体DNA在一个顺序的方式，一个寡核苷酸/寡糖结合倍的时间。POT 1从3′到5′结合，从而以逐步的方式解折叠G-四链体。相反，POT 1-TPP 1复合物诱导G-四链体的连续折叠和解折叠。我们表明，POT 1-TPP 1幻灯片来回端粒DNA和突变体端粒DNA上POT 1不能单独结合。滑动运动是POT 1-TPP 1特异性的，因为POT 1和ssDNA结合蛋白gp 32不能重现这种活性。我们的研究结果揭示了端粒结构调控的基本分子步骤和动力学。
Human telomeres possess a single-stranded DNA (ssDNA) overhang of TTAGGG repeats, which can self-fold into a G-quadruplex structure. POT1 binds specifically to the telomeric overhang and partners with TPP1 to regulate telomere lengthening and capping, although the mechanism remains elusive. Here, we show that POT1 binds stably to folded telomeric G-quadruplex DNA in a sequential manner, one oligonucleotide/oligosaccharide binding fold at a time. POT1 binds from 3′ to 5′, thereby unfolding the G-quadruplex in a stepwise manner. In contrast, the POT1-TPP1 complex induces a continuous folding and unfolding of the G-quadruplex. We demonstrate that POT1-TPP1 slides back and forth on telomeric DNA and also on a mutant telomeric DNA to which POT1 cannot bind alone. The sliding motion is specific to POT1-TPP1, as POT1 and ssDNA binding protein gp32 cannot recapitulate this activity. Our results reveal fundamental molecular steps and dynamics involved in telomere structure regulation.
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