Additional file 1 of A biophysical model of supercoiling dependent transcription predicts a structural aspect to gene regulation

Supporting Information. The SI of this paper is a brief derivations of the free energy of the DNA with supercoiling incorporated, an alternative derivation of the biophysical model with the supercoiling influencing the rate k kat and an application of Eq. 2 from the biophysical model in future studies. (PDF 237 kb

Long-Loop G‑Quadruplexes Are Misfolded Population Minorities with Fast Transition Kinetics in Human Telomeric Sequences

Single-stranded guanine (G)-rich sequences at the 3′ end of human telomeres provide ample opportunities for physiologically relevant structures, such as G-quadruplexes, to form and interconvert. Population equilibrium in this long sequence is expected to be intricate and beyond the resolution of ensemble-average techniques, such as circular dichroism, NMR, or X-ray crystallography. By combining a force-jump method at the single-molecular level and a statistical population deconvolution at the sub-nanometer resolution, we reveal a complex population network with unprecedented transition dynamics in human telomeric sequences that contain four to eight TTAGGG repeats. Our kinetic data firmly establish that G-triplexes are intermediates to G-quadruplexes while long-loop G-quadruplexes are misfolded population minorities whose formation and disassembly are faster than G-triplexes or regular G-quadruplexes. The existence of misfolded DNA supports the emerging view that structural and kinetic complexities of DNA can rival those of RNA or proteins. While G-quadruplexes are the most prevalent species in all the sequences studied, the abundance of a misfolded G-quadruplex in a particular telomeric sequence decreases with an increase in the loop length or the number of long-loops in the structure. These population patterns support the prediction that in the full-length 3′ overhang of human telomeres, G-quadruplexes with shortest TTA loops would be the most dominant species, which justifies the modeling role of regular G-quadruplexes in the investigation of telomeric structures