title: G-quadruplex formation at the 3' end of telomere DNA inhibits its extension by telomerase, polymerase and unwinding by helicase.
abstract: Telomere G-quadruplex is emerging as a promising anti-cancer target due to its inhibition to telomerase, an enzyme expressed in more than 85% tumors. Telomerase-mediated telomere extension and some other reactions require a free 3' telomere end in single-stranded form. G-quadruplex formation near the 3' end of telomere DNA can leave a 3' single-stranded tail of various sizes. How these terminal structures affect reactions at telomere end is not clear. In this work, we studied the 3' tail size-dependence of telomere extension by either telomerase or the alternative lengthening of telomere (ALT) mechanism as well as telomere G-quadruplex unwinding. We show that these reactions require a minimal tail of 8, 12 and 6 nt, respectively. Since we have shown that G-quadruplex tends to form at the farthest 3' distal end of telomere DNA leaving a tail of no more than 5 nt, these results imply that G-quadruplex formation may play a role in regulating reactions at the telomere ends and, as a result, serve as effective drug target for intervening telomere function.
authors: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, PR China.
authors: Quan
authors: Q
authors: Wang
authors: Jia-quan
authors: JQ
authors: Liu
authors: Zhao
authors: Z
authors: Chen
authors: Ke-wei
authors: KW
authors: Zheng
authors: Chang-yue
authors: CY
authors: Chen
authors: Yu-Hua
authors: YH
authors: Hao
authors: Zheng
authors: Z
authors: Tan
mesh_terms: D004247:DNA / Q000737:chemistry; D004256:DNA Polymerase I / Q000378:metabolism*; D054856:G-Quadruplexes; D053484:RecQ Helicases / Q000378:metabolism*; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000737:chemistry* / Q000378:metabolism
chemical_list: D004247:DNA; D019098:Telomerase; D004256:DNA Polymerase I; C097151:Bloom syndrome protein; D053484:RecQ Helicases