DNA self-assembly: from chirality to evolution

Abstract

Transient or long-term DNA self-assembly participates in essential genetic functions. The present review focuses on tight DNA-DNA interactions that have recently been found to play important roles in both controlling DNA higher-order structures and their topology. Due to their chirality, double helices are tightly packed into stable right-handed crossovers. Simple packing rules that are imposed by DNA geometry and sequence dictate the overall architecture of higher order DNA structures. Close DNA-DNA interactions also provide the missing link between local interactions and DNA topology, thus explaining how type II DNA topoisomerases may sense locally the global topology. Finally this paper proposes that through its influence on DNA self-assembled structures, DNA chirality played a critical role during the early steps of evolution.

Figure 1

Chiral B-DNA crossovers. (a) Right-handed crossover assembled by the mutual fit of the backbones into the major-groove; (b) Left-handed crossover assembled by major groove-major groove interaction.

Figure 2

Design of crystal lattice from DNA sequence. The cytosines (represented in blue) along the duplex sequence define the anchoring points for groove-backbone interaction. The crossing of the duplexes within the crystal lattice is therefore controlled by the DNA sequence.

Figure 3

Cytosine and DNA self-assembly. (a) Superimposed self-fitted right-handed DNA crossovers found in the Nucleic Acids Database. The cytosines involved in the interaction are represented in red and orange; (b) 5-Methyl cytosine stabilizes the groove-backbone interaction through the formation of C–H…O interactions with the phosphate group; (c) The role of the sequence in DNA self-assembly: the cytosines (represented in red) dictate the organisation of the triangular motifs.

Figure 4

DNA supramolecular construction set. The double helix imposes discrete geometric solutions for its 3D assembly into simple motifs. Representation of packing motifs formed by two helices crossing a third one, at anchoring points separated by 5 bp, 7 bp and 10 bp, respectively. An equilateral triangle is formed when the intersection points of three DNA segments are 7 bp distant.

Figure 5

DNA-DNA interactions control the assembly of the chromatin fibre. (a) The model proposes that DNA geometry and sequence contribute to organise tighly packed regions in chromatin. The GC sequences suitable to form tight DNA-DNA interactions are represented in red. The geometric constraints imposed by the groove-backbone interaction influence the overall architecture of the fibre; (b) and (c) Right-handed crossovers between nucleosomal DNA observed in their crystal structure of [47] and [48], respectively.

Figure 6

From DNA chirality to the local sensing of global topology. (a) Stable right-handed crossovers form spontaneously in relaxed, (+) supercoiled DNA or catenanes. They constitute the natural substrate of type II topoisomerases that clamp them across their large angle (middle). Thus, the topoisomerase ring does not form a topological link with the (+) supercoiled ring. The strand passage reaction generates a free configuration (top) that is consistent with the enzyme processivity; (b) Unstable left-handed crossovers are exclusively formed in (−) supercoiled DNA. Our model predicts that type II topoisomerases slightly deform and clamp them, across their large angle (middle). This imposes a different orientation in which the enzyme ring and the (−) supercoiled DNA ring are topologically linked. The strand passage reaction generates a locked configuration (top) that explains the distributive behaviour of the enzyme. The gate DNA-segment (G) and transported DNA-segment (T) are represented in red and green, respectively.

Figure 7

From chirality to genome evolution. Simple rules for DNA packaging allow multiple hierarchic levels of higher-order structure assembly.