Laboratoire Matière et Systèmes Complexes

Séminaire MSC Lundi 16 Decembre 2013 à 11h30, Batiment condorcet salle 454a :

Terence Strick

Institut Jacques Monod, Paris

Bottom-up reconstruction of DNA repair processes at single-molecule resolution

DNA damage occurs continuously and through a variety of processes, ranging from physico-chemical (eg exposure to UV light, reactive oxygen species, or carcinogens in tobacco smoke) to intrinsic (eg replicative errors). One could even argue that the rate of replicative errors — eg mutations — is under selection pressure, with insufficient errors leading to a loss of evolutive capacity and an excess of errors leading to collapse of a population. DNA repair is an intrinsically multi-step process, involving recognition of DNA damage, removal of DNA damage, and re-synthesis of intact DNA. Typically each step is thus the task of at least one protein or complex of proteins, and the way in which damage is identified and removed in a timely, reliable fashion despite the challenges of a noisy environment are unclear. However it is particularly challenging using ensemble measurements to precisely measure complex reaction kinetics such as these. Here we describe progress in the study of such complex, multicomponent systems using single-molecule techniques such as DNA nanomanipulation and single-molecule fluorescence. These methods allow us to observe the initial steps of DNA repair in real-time and thus begin building up, component by component, the multiple steps of these complex reactions.