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An Improved Model for the hTERT Promoter Quadruplex

Mutations occur at four specific sites in the hTERT promoter in >75% of glioblastomas and melanomas, but the mechanism by which the mutations affect gene expression remains unexplained. We report biophysical computational studies that show that the hTERT promoter sequence forms a novel G-quadrupl...

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Detalles Bibliográficos
Autores principales: Chaires, Jonathan B., Trent, John O., Gray, Robert D., Dean, William L., Buscaglia, Robert, Thomas, Shelia D., Miller, Donald M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4272262/
https://www.ncbi.nlm.nih.gov/pubmed/25526084
http://dx.doi.org/10.1371/journal.pone.0115580
Descripción
Sumario:Mutations occur at four specific sites in the hTERT promoter in >75% of glioblastomas and melanomas, but the mechanism by which the mutations affect gene expression remains unexplained. We report biophysical computational studies that show that the hTERT promoter sequence forms a novel G-quadruplex structure consisting of three contiguous, stacked parallel quadruplexes. The reported hTERT mutations map to the central quadruplex within this structure, and lead to an alteration of its hydrodynamic properties and stability.