Paeschke Katrin, Juranek Stefan, Simonsson Tomas, Hempel Anne, Rhodes Daniela, Lipps Hans Joachim
Institute of Cell Biology, University Witten/Herdecke, Stockumer Strasse 10, 58453 Witten, Germany.
Nat Struct Mol Biol. 2008 Jun;15(6):598-604. doi: 10.1038/nsmb.1422. Epub 2008 May 18.
The telomeric G-overhangs of the ciliate Stylonychia lemnae fold into a G-quadruplex DNA structure in vivo. Telomeric G-quadruplex formation requires the presence of two telomere end binding proteins, TEBPalpha and TEBPbeta, and is regulated in a cell-cycle dependent manner. Unfolding of this structure in S phase is dependent on the phosphorylation of TEBPbeta. Here we show that TEBPbeta phosphorylation is necessary but not sufficient for a G-quadruplex unfolding rate compatible with telomere synthesis. The telomerase seems to be actively involved in telomeric G-quadruplex DNA structure unfolding in vivo. Significantly, the telomerase is recruited to telomeres by phosphorylated TEBPbeta, and hence telomerase recruitment is cell-cycle regulated through phosphorylation. These observations allow us to propose a model for the regulation of G-quadruplex unfolding and telomere synthesis during the cell cycle.
纤毛虫莱姆斯坦尼拉的端粒G-突出端在体内折叠成G-四链体DNA结构。端粒G-四链体的形成需要两种端粒末端结合蛋白TEBPα和TEBPβ的存在，并以细胞周期依赖性方式受到调控。该结构在S期的解折叠依赖于TEBPβ的磷酸化。在这里我们表明，TEBPβ磷酸化对于与端粒合成相容的G-四链体解折叠速率是必要的，但并不充分。端粒酶似乎在体内积极参与端粒G-四链体DNA结构的解折叠。值得注意的是，端粒酶通过磷酸化的TEBPβ被招募到端粒，因此端粒酶的招募通过磷酸化受到细胞周期调控。这些观察结果使我们能够提出一个在细胞周期中调控G-四链体解折叠和端粒合成的模型。
