G-quadruplex preferentially forms at the very 3' end of vertebrate telomeric DNA.
G-quadruplex preferentially forms at the very 3' end of vertebrate telomeric DNA.
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G-四链体优先在脊椎动物端粒 DNA 的 3' 端形成。
DOI：
10.1093/nar/gkm1137
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发表时间：
2008-03
影响因子：
14.9
通讯作者：
Tan, Zheng
中科院分区：
文献类型：
--
作者：
Tang, Jun;Kan, Zhong-yuan;Yao, Yuan;Wang, Quan;Hao, Yu-hua;Tan, Zheng
人染色体末端用TTAGGG的重复序列保护。端粒DNA在复制时缩短。在大多数肿瘤细胞中，端粒的缩短被端粒酶补偿，端粒酶将端粒重复序列添加到富含G的端粒链的3′端。四个TTAGGG重复可以折叠成G-四链体，其是端粒酶的不良底物。这种特性被认为可以在体内调节端粒酶活性，通过G-四链体稳定化抑制端粒酶被认为是一种抗癌的治疗策略。理论上，G-四链体可以在沿着长的富G链的任何地方形成。G-四链体的形成决定了端粒3′端是否可以被端粒酶接近，并可能对端粒发挥的其他功能有影响。我们通过DMS足迹法和核酸外切酶水解研究了不同位置的G-四链体形成。我们发现，G-四链体优先形成在3′端比在内部位置。这一特性为G-四链体抑制端粒酶提供了分子基础。此外，它还可以调节端粒3′端的结构，如端粒的交替延长机制、端粒T环的形成、端粒末端的保护和端粒DNA的复制等。因此，靶向端粒G-四链体可能比简单地抑制端粒酶影响更多的端粒功能。
Human chromosome ends are protected with kilobases repeats of TTAGGG. Telomere DNA shortens at replication. This shortening in most tumor cells is compensated by telomerase that adds telomere repeats to the 3′ end of the G-rich telomere strand. Four TTAGGG repeats can fold into G-quadruplex that is a poor substrate for telomerase. This property has been suggested to regulate telomerase activity in vivo and telomerase inhibition via G-quadruplex stabilization is considered a therapeutic strategy against cancer. Theoretically G-quadruplex can form anywhere along the long G-rich strand. Where G-quadruplex forms determines whether the 3′ telomere end is accessible to telomerase and may have implications in other functions telomere plays. We investigated G-quadruplex formation at different positions by DMS footprinting and exonuclease hydrolysis. We show that G-quadruplex preferentially forms at the very 3′ end than at internal positions. This property provides a molecular basis for telomerase inhibition by G-quadruplex formation. Moreover, it may also regulate those processes that depend on the structure of the very 3′ telomere end, for instance, the alternative lengthening of telomere mechanism, telomere T-loop formation, telomere end protection and the replication of bulky telomere DNA. Therefore, targeting telomere G-quadruplex may influence more telomere functions than simply inhibiting telomerase.
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影响因子：
4.8
作者：
Enokizono, Y;Konishi, Y;Katahira, M
通讯作者：
Katahira, M
G-四链体配体与人染色体末端的优先结合。
影响因子：
14.9
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
通讯作者：
Boussin, FD
影响因子：
7.4
作者：
Cao, ZH;Huang, CC;Tan, WH
通讯作者：
Tan, WH
影响因子：
10.5
作者：
Duquette, ML;Handa, P;Maizels, N
通讯作者：
Maizels, N
影响因子：
15
作者：
Han, FXG;Wheelhouse, RT;Hurley, LH
通讯作者：
Hurley, LH