Experimental and theoretical studies of sequence effects on the fluctuation and melting of short DNA molecules

TL;DR

This study combines experiments and theory to analyze how sequence effects influence the fluctuation and melting behavior of short DNA molecules, revealing non-local effects of AT-rich regions on DNA stability.

Contribution

It introduces a new experimental method for mapping DNA opening and modifies a mesoscopic model to incorporate non-local sequence effects.

Findings

AT-rich regions influence base pair opening up to 10 base pairs away

Modified model accurately describes melting behavior of specific DNA sequences

Non-local effects are significant in DNA fluctuation and melting processes

Abstract

Understanding the melting of short DNA sequences probes DNA at the scale of the genetic code and raises questions which are very different from those posed by very long sequences, which have been extensively studied. We investigate this problem by combining experiments and theory. A new experimental method allows us to make a mapping of the opening of the guanines along the sequence as a function of temperature. The results indicate that non-local effects may be important in DNA because an AT-rich region is able to influence the opening of a base pair which is about 10 base pairs away. An earlier mesoscopic model of DNA is modified to correctly describe the time scales associated to the opening of individual base pairs well below melting, and to properly take into account the sequence. Using this model to analyze some characteristic sequences for which detailed experimental data on the melting is available [Montrichok et al. 2003 Europhys. Lett. {\bf 62} 452], we show that we have to introduce non-local effects of AT-rich regions to get acceptable results. This brings a second indication that the influence of these highly fluctuating regions of DNA on their neighborhood can extend to some distance.