title: G-quadruplex preferentially forms at the very 3' end of vertebrate telomeric DNA.
abstract: Human chromosome ends are protected with kilobases repeats of TTAGGG. Telomere DNA shortens at replication. This shortening in most tumor cells is compensated by telomerase that adds telomere repeats to the 3' end of the G-rich telomere strand. Four TTAGGG repeats can fold into G-quadruplex that is a poor substrate for telomerase. This property has been suggested to regulate telomerase activity in vivo and telomerase inhibition via G-quadruplex stabilization is considered a therapeutic strategy against cancer. Theoretically G-quadruplex can form anywhere along the long G-rich strand. Where G-quadruplex forms determines whether the 3' telomere end is accessible to telomerase and may have implications in other functions telomere plays. We investigated G-quadruplex formation at different positions by DMS footprinting and exonuclease hydrolysis. We show that G-quadruplex preferentially forms at the very 3' end than at internal positions. This property provides a molecular basis for telomerase inhibition by G-quadruplex formation. Moreover, it may also regulate those processes that depend on the structure of the very 3' telomere end, for instance, the alternative lengthening of telomere mechanism, telomere T-loop formation, telomere end protection and the replication of bulky telomere DNA. Therefore, targeting telomere G-quadruplex may influence more telomere functions than simply inhibiting telomerase.
authors.affiliation: Laboratory of Biochemistry and Biophysics, College of Life Sciences, Wuhan University, Wuhan 430072, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Tang
authors.forename: Zhong-Yuan
authors.initials: ZY
authors.lastname: Kan
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yao
authors.forename: Quan
authors.initials: Q
authors.lastname: Wang
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Hao
authors.forename: Zheng
authors.initials: Z
authors.lastname: Tan
mesh_terms: D004247:DNA / Q000737:chemistry / Q000378:metabolism; D018983:DNA Footprinting; D005090:Exodeoxyribonucleases / Q000378:metabolism; D054856:G-Quadruplexes; D006801:Humans; D012091:Repetitive Sequences, Nucleic Acid; D016615:Telomere / Q000737:chemistry*
chemical_list: D004247:DNA; D005090:Exodeoxyribonucleases