title: An improved model for the hTERT promoter quadruplex.
abstract: 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.
authors.affiliation: James Graham Brown Cancer Center, Department of Medicine, University of Louisville, Louisville, Kentucky, United States of America.
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Chaires
authors.affiliation: James Graham Brown Cancer Center, Department of Medicine, University of Louisville, Louisville, Kentucky, United States of America.
authors.forename: John O
authors.initials: JO
authors.lastname: Trent
authors.affiliation: James Graham Brown Cancer Center, Department of Medicine, University of Louisville, Louisville, Kentucky, United States of America.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Gray
authors.affiliation: James Graham Brown Cancer Center, Department of Medicine, University of Louisville, Louisville, Kentucky, United States of America.
authors.forename: William L
authors.initials: WL
authors.lastname: Dean
authors.affiliation: James Graham Brown Cancer Center, Department of Medicine, University of Louisville, Louisville, Kentucky, United States of America.
authors.forename: Robert
authors.initials: R
authors.lastname: Buscaglia
authors.affiliation: James Graham Brown Cancer Center, Department of Medicine, University of Louisville, Louisville, Kentucky, United States of America.
authors.forename: Shelia D
authors.initials: SD
authors.lastname: Thomas
authors.affiliation: James Graham Brown Cancer Center, Department of Medicine, University of Louisville, Louisville, Kentucky, United States of America.
authors.forename: Donald M
authors.initials: DM
authors.lastname: Miller
mesh_terms: D001483:Base Sequence; D002942:Circular Dichroism; D019295:Computational Biology / Q000379:methods; D054856:G-Quadruplexes; D006801:Humans; D057446:Hydrodynamics; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009154:Mutation; D011401:Promoter Regions, Genetic; D019098:Telomerase / Q000737:chemistry* / Q000235:genetics
chemical_list: C509186:TERT protein, human; D019098:Telomerase