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G-quadruplex formation at the 3′ end of telomere DNA inhibits its extension by telomerase, polymerase and unwinding by helicase

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 th...

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Detalles Bibliográficos
Autores principales: Wang, Quan, Liu, Jia-quan, Chen, Zhao, Zheng, Ke-wei, Chen, Chang-yue, Hao, Yu-hua, Tan, Zheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3152327/
https://www.ncbi.nlm.nih.gov/pubmed/21441540
http://dx.doi.org/10.1093/nar/gkr164
Descripción
Sumario: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.