Mechanical properties of single molecules: a theoretical approach.

The substantial homogeneity and the consequent conformational degeneracy of the nucleotide residues along DNA double helix have allowed great progress in the knowledge of the molecular mechanisms that control the functional organization of the genome. DNA plays a crucial role in the management of the informational content that the nucleotide sequence holds. Inside the cell, DNA actively interacts with proteins involved in replication, transcription, repair, and regulation processes. During these processes, the DNA transforms between packed and unpacked architectures, like that of chromatin or other higher-order structures morphing into shapes with structural spikes alternative to the canonical B-form in connection with biological events as in replication bubbles, hairpins or in G-quadruplex structures. The base sequence encodes the dynamics of these transformations from the atomic to the nanometer scale length, and over higher spatial scales. In fact, although an important part of the DNA informational content acts locally, it exerts its functions as collective properties of relatively long sequences and manifests as static and dynamic curvature. Such superstructural features are an intrinsic property of the sequence and are recognized and amplified by protein binding. This large-scale structural amplification influences in deterministic way DNA high scale functions by integrating sequence-dependent curvature effects and local binding of different factors.