Research on dsDNA bubble formation using Breathing DNA model

Abstract

The double-stranded(ds) DNA bending over scales of 10~100nm, among the many characteristic, plays a key role in many cellular processes, as packing on nucleosome, transcription control step and viral genome packing. Furthermore, recent experiments have shown the double-stranded (ds) DNAs readily bend and loop over the scale muchshorter than their persistence length (50 nm). In an effort to unveil this seemingly surprising phenomenon, via the Langevin dynamics simulation of our Breathing DNA model, we observe the formation of bubbles within the duplex and also forks at the ends, with the size distributions independent of the contour length. We find that these local denaturations at a physiological temperature, despite their rare and transient presence, can lower the persistence length drastically for a short DNA segment in agreement with experiment.To study the emergence of local denaturation (bubbles and forks) which affect the flexibility of the duplex, we use the Breathing DNA model simulation. In short ds DNA loops, we analyze the bubble size distributions and the melting curves for varying contour lengths, which are critically compared with those of linear DNA of the same lengths. We analytically evaluate the free energies associated with double-strand bending and single-strand bubble formation to explain the simulation data. It is found that in shorter looped DNA the bubbles are more easily initiated and formed to release the large bending energy, giving rise to melting at a lower temperature and a lower contour length.Also, in a short DNA with D-geometry(a hybrid of a circular single strand and a complementary linear strand), we study the effect of local denaturation due to the bending stress. The FRET measurement has suggested the extension of the ds part transforms from a single state into two states, depending upon the circular length. To understand this phenomenon, we study the presence of open base-pairs along the ds part as a function of ds extension, by simulating the model. We find that the two states are due to emergence of local denaturation in the middle and ends of the ds, namely a bubble and two forks, respectively. We also estimate the size of the bubble and forks and critical tension for the bifurcation, combining the experimental data with the theoretical results for the free energy landscapes. It suggests that, in such short DNA subject to a high tension, a uniformly bent state with transient bubbles coexists with a kinked state with a permanent bubble. A double-stranded DNA (dsDNA) is a linear array of AT and GC base pairs(bp). In vivo, the DNA has many repetitive sequence parts called satellites of the size ranging widely from 1 to171 bp. In this work, we study the effects of this satellite size on DNA local melting via the Ising model. As the block sizes of AT base pairs gets larger the bubble number as well as the open base pairs increases. These results are in a reasonable agreement with simulation results using the Breathing DNA model. We find that for the optimal value of the satellite size, which is 6~12 bp long, the average bubble size is smallest, meaning that double stranded structures are most stable in a certain way.