title: Telomere G-Quadruplex as a Potential Target to Accelerate Telomere Shortening by Expanding the Incomplete End-Replication of Telomere DNA.
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.
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, P.R. China. z.tan@ioz.ac.cn.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Tan
authors.forename: Jun
authors.initials: J
authors.lastname: Tang
authors.forename: Zhong-Yuan
authors.initials: ZY
authors.lastname: Kan
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Hao
mesh_terms: D004247:DNA / Q000096:biosynthesis* / Q000737:chemistry; D004261:DNA Replication; D054856:G-Quadruplexes; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016615:Telomere / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D059506:Telomere Shortening
chemical_list: D004247:DNA