High Base Pair Opening Rates in Tracts of GC Base Pairs

Dornberger, Utz; Leijon, Mikael; Fritzsche, H.

doi:10.1074/jbc.274.11.6957

Cited by 149 publications

(178 citation statements)

References 30 publications

Supporting

Mentioning

157

Contrasting

Unclassified

Order By: Relevance

“…However, we should bear in mind that ξ not only determines the definition of 'open' and 'closed', but also determines the ensemble via Eqs. (5,6). Considering Eq.…”

Section: Denaturation Curvesmentioning

confidence: 99%

“…The sequence specific order is also important. Specific sequences can reveal a high opening rate despite a high fraction of GC base-pairs [6]. Besides the already mentioned UV absorbance experiments, many ingenious techniques have been devised to study the denaturation process and the statistical and dynamical properties of DNA bubbles in general.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Bubbles and denaturation in DNA

2006

View full text Add to dashboard Cite

Abstract. The local opening of DNA is an intriguing phenomenon from a statistical physics point of view, but is also essential for its biological function. For instance, the transcription and replication of our genetic code can not take place without the unwinding of the DNA double helix. Although these biological processes are driven by proteins, there might well be a relation between these biological openings and the spontaneous bubble formation due to thermal fluctuations. Mesoscopic models, like the Peyrard-BishopDauxois model, have fairly accurately reproduced some experimental denaturation curves and the sharp phase transition in the thermodynamic limit. It is, hence, tempting to see whether these models could be used to predict the biological activity of DNA. In a previous study, we introduced a method that allows to obtain very accurate results on this subject, which showed that some previous claims in this direction, based on molecular dynamics studies, were premature. This could either imply that the present PBD should be improved or that biological activity can only be predicted in a more complex frame work that involves interactions with proteins and super helical stresses. In this article, we give detailed description of the statistical method introduced before. Moreover, for several DNA sequences, we give a thorough analysis of the bubble-statistics as function of position and bubble size and the so-called l-denaturation curves that can be measured experimentally. These show that some important experimental observations are missing in the present model. We discuss how the present model could be improved. PACS

show abstract

“…However, we should bear in mind that ξ not only determines the definition of 'open' and 'closed', but also determines the ensemble via Eqs. (5,6). Considering Eq.…”

Section: Denaturation Curvesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Bubbles and denaturation in DNA

2006

View full text Add to dashboard Cite

show abstract

“…Those curves are easy to record experimentally because the UV absorbance of a DNA solution increases drastically when the bases are unstacked, which is [3,4] managed to get some data on the melting process of short DNA sequences, detecting whether they open at one end or by starting with an open bubble in the centre. The kinetics of proton-deuterium exchange for the protons involved in the hydrogen bonds within pairs, coupled with NMR studies to detect the location of the exchanged protons, can also provide partial information on the spatial aspect of DNA fluctuations, at the expense of heavy experiments [5]. Another approach relies on special molecular constructs which attach a fluorophore and a quencher to DNA to detect its local opening at a particular site [6,7].…”

mentioning

confidence: 99%

Adding a new dimension to DNA melting curves

2009

View full text Add to dashboard Cite

Abstract. -Standard DNA melting curves record the separation of the two strands versus temperature, but they do not provide any information on the location of the opening. We introduce an experimental method which adds a new dimension to the melting curves of short DNA sequences by allowing us to record the degree of opening in several positions along the molecule all at once. This adds the spatial dimension to the melting curves and allows a precise investigation of the role of the base-pair sequence on the fluctuations and denaturation of the DNA double helix. We illustrate the power of the method by investigating the influence of an AT rich region on the fluctuations of neighboring domains.DNA melting, i.e. the separation of the two strands of the double helix, and its reverse process hybridisation are ubiquitous in biology, in vivo for instance for DNA transcription in the reading of the genetic code of a gene, as well as in vitro in biological laboratories for PCR (Polymerase Chain Reaction) or the use of DNA microarrays. This is why DNA melting has been extensively studied even in the early days of DNA structural studies [1]. An approximate understanding of the melting curves of long DNA segments, with thousands of base pairs, can be provided by simple statistical physics models, using empirical parameters because, at this large scale, the subtle effects of the base pair sequence are smoothed out. Understanding the fluctuations and melting of short DNA fragments of a few tens of base pairs with a high degree of heterogeneity is much more challenging. And it is also very important because this size is the scale at which the genetic code can be resolved. This would have some significant biological consequences to unravel the processes by which specific binding sites are recognised by proteins, drugs, mutagens and other molecules. This would also have a lot of practical importance in the design of the PCR primers which are used everyday in most of the biological laboratories [2].The two kind of base pairs which exist in the DNA double helix have different thermal stability, the AT pair, bound by two hydrogen bonds, being weaker than the GC pair bound by three hydrogen bonds. This explains why the melting curve of a heterogeneous DNA sequence, which shows the fraction of open pairs as a function of temperature, can exhibit complex features. Those curves are easy to record experimentally because the UV absorbance of a DNA solution increases drastically when the bases are unstacked, which is (a) Mailing

show abstract

“…It has been shown that homosequence DNA denatures quite abruptly within a very small temperature interval, whereas heterosequence DNA denatures via a few partial denaturation states [22,38], leading to a denaturation curve (plot of average number of open bp's against temperature) whose shape is highly sensitive to the sequence. The melting and its transition do not only depend on the fraction of strong G-C or A-T bonds, but are also sequence specific [39]. This phenomena has been recently suggested as an application for DNA sequencing [40].…”

Section: Denaturation Of Diblock Dnamentioning

confidence: 99%

Sufficient minimal model for DNA denaturation: Integration of harmonic scalar elasticity and bond energies

Singh

Granek

2016

The Journal of Chemical Physics

View full text Add to dashboard Cite

We study DNA denaturation by integrating elasticity — as described by the Gaussian network model — with bond binding energies, distinguishing between different base pairs and stacking energies. We use exact calculation, within the model, of the Helmholtz free-energy of any partial denaturation state, which implies that the entropy of all formed “bubbles” (“loops”) is accounted for. Considering base pair bond removal single events, the bond designated for opening is chosen by minimizing the free-energy difference for the process, over all remaining base pair bonds. Despite of its great simplicity, for several known DNA sequences our results are in accord with available theoretical and experimental studies. Moreover, we report free-energy profiles along the denaturation pathway, which allow to detect stable or meta-stable partial denaturation states, composed of bubble, as local free-energy minima separated by barriers. Our approach allows to study very long DNA strands with commonly available computational power, as we demonstrate for a few random sequences in the range 200-800 base-pairs. For the latter, we also elucidate the self-averaging property of the system. Implications for the well known breathing dynamics of DNA are elucidated.

show abstract

High Base Pair Opening Rates in Tracts of GC Base Pairs

Cited by 149 publications

References 30 publications

Bubbles and denaturation in DNA

Bubbles and denaturation in DNA

Adding a new dimension to DNA melting curves

Sufficient minimal model for DNA denaturation: Integration of harmonic scalar elasticity and bond energies

Contact Info

Product

Resources

About