Tan Zheng, Tang Jun, Kan Zhong-Yuan, Hao Yu-Hua
State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, P.R. China.
Curr Top Med Chem. 2015;15(19):1940-6. doi: 10.2174/1568026615666150515145552.
Chromosomes in human cells are protected by telomeres. Telomere shortens during each round of cell division because of the DNA end-replication problem. Cancer cells maintain telomere length homeostasis by either telomerase or/and the alternative lengthening of telomere (ALT) mechanism to sustain their division potential. Telomeric DNA tends to form G-quadruplex preferentially at the extreme 3' end. This unique feature prevents the 3' end from being used as a substrate of telomerase and as a primer in the ALT. Therefore, stabilizing telomere G-quadruplex is expected to inhibit both pathways and limit the proliferation of cancer cells. Based on a mathematical modeling and experimental results, this mini-review proposes a hypothesis that the formation of G-quadruplex in telomere may constitute a significant contribution to the incomplete end-replication of telomere DNA by preventing the priming of DNA synthesis near the 3' end during telomere replication. According to this, stabilization of telomere G-quadruplex by chemical ligand may promise to accelerate telomere shortening in proliferating cells.
人类细胞中的染色体由端粒保护。由于DNA末端复制问题，端粒在每一轮细胞分裂过程中都会缩短。癌细胞通过端粒酶或/和端粒替代延长（ALT）机制维持端粒长度稳态，以维持其分裂潜能。端粒DNA倾向于在极端3'端优先形成G-四链体。这一独特特征可防止3'端用作端粒酶的底物以及ALT中的引物。因此，稳定端粒G-四链体有望抑制这两种途径并限制癌细胞的增殖。基于数学建模和实验结果，本综述提出了一个假设，即端粒中G-四链体的形成可能通过在端粒复制过程中阻止3'端附近的DNA合成引发，从而对端粒DNA的不完全末端复制做出重大贡献。据此，化学配体稳定端粒G-四链体可能有望加速增殖细胞中端粒的缩短。
