Helical Chirality: a Link between Local Interactions and Global Topology in DNA

Youri Timsit,Péter Várnai

doi:10.1371/journal.pone.0009326

Abstract

DNA supercoiling plays a major role in many cellular functions. The global DNA conformation is however intimately linked to local DNA-DNA interactions influencing both the physical properties and the biological functions of the supercoiled molecule. Juxtaposition of DNA double helices in ubiquitous crossover arrangements participates in multiple functions such as recombination, gene regulation and DNA packaging. However, little is currently known about how the structure and stability of direct DNA-DNA interactions influence the topological state of DNA. Here, a crystallographic analysis shows that due to the intrinsic helical chirality of DNA, crossovers of opposite handedness exhibit markedly different geometries. While right-handed crossovers are self-fitted by sequence-specific groove-backbone interaction and bridging Mg2+ sites, left-handed crossovers are juxtaposed by groove-groove interaction. Our previous calculations have shown that the different geometries result in differential stabilisation in solution, in the presence of divalent cations. The present study reveals that the various topological states of the cell are associated with different inter-segmental interactions. While the unstable left-handed crossovers are exclusively formed in negatively supercoiled DNA, stable right-handed crossovers constitute the local signature of an unusual topological state in the cell, such as the positively supercoiled or relaxed DNA. These findings not only provide a simple mechanism for locally sensing the DNA topology but also lead to the prediction that, due to their different tertiary intra-molecular interactions, supercoiled molecules of opposite signs must display markedly different physical properties. Sticky inter-segmental interactions in positively supercoiled or relaxed DNA are expected to greatly slow down the slithering dynamics of DNA. We therefore suggest that the intrinsic helical chirality of DNA may have oriented the early evolutionary choices for DNA topology.

Highlights

The topology of DNA is finely tuned by topoisomerases [1] and plays a major role in many cellular processes in both prokaryotes and eukaryotes, such as remote gene regulation and site-specific recombination [2,3]
We demonstrate that due to the intrinsic helical chirality of DNA, the global topological state of DNA is asymmetrically encoded in the geometry and stability of DNA crossovers
In showing that the chiral nature of the B-DNA helix profoundly affects the physical properties of the superhelices of opposite signs, our study provides new clues that may contribute to understand the early evolutionary choices for a particular DNA topology in the cellular environment

Summary

Introduction

The topology of DNA is finely tuned by topoisomerases [1] and plays a major role in many cellular processes in both prokaryotes and eukaryotes, such as remote gene regulation and site-specific recombination [2,3]. In right-handed crossovers that are characterized by positive values of the crossing angle, the double helices can be mutually self-fitted by groove-backbone interaction. Crystal packing of DNA crossovers has provided structural examples of more complex chiral motifs such as the heart of trefoil knots of opposite signs (Fig. 3) [36].

Results

Conclusion