Coexistence of two distinct G-quadruplex conformations in the hTERT promoter.
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.
Lim
Kah Wai
KW
School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore.
Lacroix
Laurent
L
Yue
Doris Jia En
DJ
Lim
Joefina Kim Cheow
JK
Lim
Jocelyn Mei Wen
JM
Phan
Anh Tuân
AT
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
C509186:TERT protein, human; D019098:Telomerase