Preferential binding of a G-quadruplex ligand to human chromosome ends.
Preferential binding of a G-quadruplex ligand to human chromosome ends.
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G-四链体配体与人染色体末端的优先结合。
DOI：
10.1093/nar/gki722
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发表时间：
2005
影响因子：
14.9
通讯作者：
Boussin, FD
中科院分区：
文献类型：
--
作者：
Granotier, C;Pennarun, G;Riou, L;Hoffschir, F;Gauthier, LR;De Cian, A;Gomez, D;Mandine, E;Riou, JF;Mergny, JL;Mailliet, P;Dutrillaux, B;Boussin, FD
端粒的G突出端被认为采用特定的构象，如T环或G四链体。已经提出，G-四链体结构可以通过特异性配体稳定，这是一种新的癌症治疗方法，包括抑制端粒酶，端粒酶是一种参与端粒维持和细胞永生的酶。虽然G-四链体的形成在多年前就在体外得到了证实，但它还没有在活的人类细胞中得到明确的证实。因此，我们研究了氚标记的G-四链体配体，3 H-360 A（2，6-N，N′-甲基-喹啉-3-基）-吡啶二甲酰胺[甲基-3H]的染色体结合。我们通过平衡透析验证了3 H-360 A对G-四链体结构的体外选择性。然后，我们通过与人类基因组DNA的结合实验表明，3 H-360 A对端粒3′-突出端的G-四链体结构具有非常有效的选择性。最后，我们对用3 H-360 A培养的细胞的中期涂片进行了放射自显影。我们发现，3 H-360 A优先结合到人正常（外周血淋巴细胞）和肿瘤细胞（T98 G和CEM 1301）的染色体末端区域。总之，我们的研究结果提供了证据表明，一个特定的G-四链体配体与人类染色体的末端相互作用。它们支持G-四链体配体诱导和/或稳定人细胞端粒处的G-四链体结构的假设。
The G-overhangs of telomeres are thought to adopt particular conformations, such as T-loops or G-quadruplexes. It has been suggested that G-quadruplex structures could be stabilized by specific ligands in a new approach to cancer treatment consisting in inhibition of telomerase, an enzyme involved in telomere maintenance and cell immortality. Although the formation of G-quadruplexes was demonstrated in vitro many years ago, it has not been definitively demonstrated in living human cells. We therefore investigated the chromosomal binding of a tritiated G-quadruplex ligand, 3H-360A (2,6-N,N′-methyl-quinolinio-3-yl)-pyridine dicarboxamide [methyl-3H]. We verified the in vitro selectivity of 3H-360A for G-quadruplex structures by equilibrium dialysis. We then showed by binding experiments with human genomic DNA that 3H-360A has a very potent selectivity toward G-quadruplex structures of the telomeric 3′-overhang. Finally, we performed autoradiography of metaphase spreads from cells cultured with 3H-360A. We found that 3H-360A was preferentially bound to chromosome terminal regions of both human normal (peripheral blood lymphocytes) and tumor cells (T98G and CEM1301). In conclusion, our results provide evidence that a specific G-quadruplex ligand interacts with the terminal ends of human chromosomes. They support the hypothesis that G-quadruplex ligands induce and/or stabilize G-quadruplex structures at telomeres of human cells.
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影响因子：
10.5
作者：
Duquette, ML;Handa, P;Maizels, N
通讯作者：
Maizels, N
影响因子：
14.9
作者：
Phan, AT;Mergny, JL
通讯作者：
Mergny, JL
DOI：
10.1073/pnas.052698099
发表时间：
2002-03-05
影响因子：
11.1
作者：
Riou, JF;Guittat, L;Mergny, JL
通讯作者：
Mergny, JL
影响因子：
8.4
作者：
Shay, JW;Bacchetti, S
通讯作者：
Bacchetti, S
影响因子：
11.2
作者：
Burger, AM;Dai, FP;Neidle, S
通讯作者：
Neidle, S