Telomere G-Quadruplex as a Potential Target to Accelerate Telomere Shortening by Expanding the Incomplete End-Replication of Telomere DNA

Title:Telomere G-Quadruplex as a Potential Target to Accelerate Telomere Shortening by Expanding the Incomplete End-Replication of Telomere DNA

Volume: 15 Issue: 19

Author(s): Zheng Tan, Jun Tang, Zhong-Yuan Kan and Yu-Hua Hao

Affiliation:

Keywords: Cancer, DNA replication, G-quadruplex, Proliferative potential, Telomere extension, Telomere shortening.

Abstract: 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.

Cite this article as:

Tan Zheng, Tang Jun, Kan Zhong-Yuan and Hao Yu-Hua, Telomere G-Quadruplex as a Potential Target to Accelerate Telomere Shortening by Expanding the Incomplete End-Replication of Telomere DNA, Current Topics in Medicinal Chemistry 2015; 15 (19) . https://dx.doi.org/10.2174/1568026615666150515145552