G-quadruplex formation in human telomeric (TTAGGG)4 sequence with complementary strand in close vicinity under molecularly crowded condition.
Chromosomes in vertebrates are protected at both ends by telomere DNA composed of tandem (TTAGGG)n repeats. DNA replication produces a blunt-ended leading strand telomere and a lagging strand telomere carrying a single-stranded G-rich overhang at its end. The G-rich strand can form G-quadruplex structure in the presence of K+ or Na+. At present, it is not clear whether quadruplex can form in the double-stranded telomere region where the two complementary strands are constrained in close vicinity and quadruplex formation, if possible, has to compete with the formation of the conventional Watson-Crick duplex. In this work, we studied quadruplex formation in oligonucleotides and double-stranded DNA containing both the G- and C-rich sequences to better mimic the in vivo situation. Under such competitive condition only duplex was observed in dilute solution containing physiological concentration of K+. However, quadruplex could preferentially form and dominate over duplex structure under molecular crowding condition created by PEG as a result of significant quadruplex stabilization and duplex destabilization. This observation suggests quadruplex may potentially form or be induced at the blunt end of a telomere, which may present a possible alternative form of structures at telomere ends.
Kan
Zhong-yuan
ZY
Laboratory of Biochemistry and Biophysics, College of Life Sciences, College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, PR China.
Lin
Yi
Y
Wang
Feng
F
Zhuang
Xin-ying
XY
Zhao
Yong
Y
Pang
Dai-wen
DW
Hao
Yu-hua
YH
Tan
Zheng
Z
D001483:Base Sequence; D003553:Cystine / Q000737:chemistry; D004247:DNA / Q000737:chemistry* / Q000648:ultrastructure; D054856:G-Quadruplexes; D006147:Guanine / Q000737:chemistry; D006801:Humans; D018625:Microscopy, Atomic Force; D011092:Polyethylene Glycols / Q000737:chemistry; D020080:Tandem Repeat Sequences; D016615:Telomere / Q000737:chemistry*
D011092:Polyethylene Glycols; D003553:Cystine; D006147:Guanine; D004247:DNA