Telomere end-binding proteins control the formation of G-quadruplex DNA structures in vivo
Telomere end-binding proteins control the formation of G-quadruplex DNA structures in vivo
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DOI：
10.1038/nsmb982
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发表时间：
2005-10-01
影响因子：
16.8
通讯作者：
Lipps, HJ
中科院分区：
文献类型：
--
作者：
Paeschke, K;Simonsson, T;Lipps, HJ
端粒末端结合蛋白（TEBP）与端粒的富含鸟嘌呤的突出端（G-突出端）结合。虽然TEBPs的DNA结合特性已在体外研究，很少有人知道它们在体内的功能。在这里，我们使用RNA干扰，以探讨在体内功能的两个纤毛虫TEBP，TEBP α和TEBP β。沉默编码两种TEBP的基因的表达表明，它们在体内合作控制端粒处的反平行鸟嘌呤四链体（G-四链体）DNA结构的形成。这种功能似乎取决于TEBP α在细胞核中附着端粒和将TEBP β募集到这些位点中的作用。体外DNA结合和足迹研究证实了体内观察结果，并强调了TEBP β的C末端在G-四链体形成中的作用。我们还发现体内G-四链体的形成受TEBP β的细胞周期依赖性磷酸化调节。
Telomere end-binding proteins (TEBPs) bind to the guanine-rich overhang (G-overhang) of telomeres. Although the DNA binding properties of TEBPs have been investigated in vitro, little is known about their functions in vivo. Here we use RNA interference to explore in vivo functions of two ciliate TEBPs, TEBP alpha and TEBP beta. Silencing the expression of genes encoding both TEBPs shows that they cooperate to control the formation of an antiparallel guanine quadruplex (G-quadruplex) DNA structure at telomeres in vivo. This function seems to depend on the role of TEBP alpha in attaching telomeres in the nucleus and in recruiting TEBP beta to these sites. In vitro DNA binding and footprinting studies confirm the in vivo observations and highlight the role of the C terminus of TEBP beta in G-quadruplex formation. We have also found that G-quadruplex formation in vivo is regulated by the cell cycle-dependent phosphorylation of TEBP beta.