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

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

Journal Name: Current Topics in Medicinal Chemistry

Volume 15 , Issue 19 , 2015

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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.

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

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Article Details

VOLUME: 15
ISSUE: 19
Year: 2015
Page: [1940 - 1946]
Pages: 7
DOI: 10.2174/1568026615666150515145552

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