Supercoiling-induced structural dynamics of DNA defects

Rustico 2nd Floor, Seminar Room

Strada delle Tabarelle, 286
Trento - Italy

In the cellular environment, DNA is frequently subject to supercoiling and looping, phenomena that impact its activity across a wide range of biological functions. In particular, negative supercoiling induces mechanical stress along the DNA backbone, which may result in localized disruptions in base pairing at distant sites. Such disruptions can induce sharp bending at specific regions, thereby facilitating DNA to relieve torsional strain, a mechanism that is reckoned to be essential for structural maintenance and genomic stability.

In this presentation, I will show the complex structural dynamics of small circular DNA molecules. In particular, I assess the occurrence and behavior of DNA bubbles—molecular regions where the DNA is locally melted—focusing on both the thermodynamics and the kinetic behavior associated with the denaturation events. I discuss the impact of topological constraints and DNA sequence-dependent effects which can affect the structural evolution of the molecule, thereby highlighting possibile implications in the context of DNA-protein binding.

In the last part, I will present the impact of DNA mismatches—common form of DNA defect that can be modeled as an enforced DNA bubble—on the DNA structure. Here, I will show how DNA mismatches may induce conformational rearrangements at molecular level to segregate DNA defects at apical loop regions, i.e. DNA locations that might provide effective biding sites in the context of enzymatic repair.

People

  • Manuel Micheloni - Speaker
    UNITN

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