title: Coexistence of two distinct G-quadruplex conformations in the hTERT promoter.
abstract: The catalytic subunit of human telomerase, hTERT, actively elongates the 3' end of the telomere in most cancer cells. The hTERT promoter, which contains many guanine-rich stretches on the same DNA strand, exhibits an exceptional potential for G-quadruplex formation. Here we show that one particular G-rich sequence in this region coexists in two G-quadruplex conformations in potassium solution: a (3 + 1) and a parallel-stranded G-quadruplexes. We present the NMR solution structures of both conformations, each comprising several robust structural elements, among which include the (3 + 1) and all-parallel G-tetrad cores, single-residue double-chain-reversal loops, and a capping A.T base pair. A combination of NMR and CD techniques, complemented with sequence modifications and variations of experimental condition, allowed us to better understand the coexistence of the two G-quadruplex conformations in equilibrium and how different structural elements conspire to favor a particular form.
authors: School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore.
authors: Kah Wai
authors: KW
authors: Lim
authors: Laurent
authors: L
authors: Lacroix
authors: Doris Jia En
authors: DJ
authors: Yue
authors: Joefina Kim Cheow
authors: JK
authors: Lim
authors: Jocelyn Mei Wen
authors: JM
authors: Lim
authors: Anh Tuân
authors: AT
authors: Phan
mesh_terms: D055162:Biocatalysis; D054856:G-Quadruplexes; D020862:GC Rich Sequence; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D009690:Nucleic Acid Conformation; D011401:Promoter Regions, Genetic; D019098:Telomerase / Q000737:chemistry* / Q000378:metabolism; D016615:Telomere / Q000737:chemistry
chemical_list: C509186:TERT protein, human; D019098:Telomerase