Book of Abstracts: Albany 2007
June 19-23 2007
Quadruplexes of Human Telomere DNA
Secondary structures of the G-rich strand of human telomere DNA fragments G3(TTAG3)n, n=1-16, have been studied by means of CD spectroscopy and polyacrylamide gel electrophoresis, in solutions of physiological potassium cation concentrations. It has been found that folding of these fragments into quadruplexes as well as quadruplex thermostabilities and enthalpy values depend on the number of TTAG3 repeats as well as on the presence of flanking sequences. The suggested topologies include, for example, antiparallel and parallel bimolecular quadruplexes, an intramolecular antiparallel quadruplex, a quadruplex consisting of three parallel chains and one antiparallel chain, a poorly stable parallel intramolecular quadruplex, and both parallel and antiparallel tetramolecular quadruplexes. G3(TTAG3)3 folds into a single, stable, and very compact intramolecular quadruplex. With an increasing repeat number, the fragment quadruplexes surprisingly are ever less thermostable and their migration and enthalpy decrease. The enthalpy decrease is not gradual, but proceeds in jumps at integer multiplies of four G3 blocks. This led us to suggestion (1), that the single stranded human telomere overhang has a nucleosome-like architecture of beads on a string. The basic unit -- the bead is represented by the intramolecular quadruplex formed by three guanine tetrads. These properties may contribute to elucidation of the stepwise telomere shortening.
References and Footnotes
Institute of Biophysics