Regensburg 2010 – wissenschaftliches Programm
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SOE: Fachverband Physik sozio-ökonomischer Systeme
SOE 10: Evolutionary Game Theory III (with BP)
SOE 10.1: Hauptvortrag
Dienstag, 23. März 2010, 14:00–14:30, H44
Stochasticity and specificity in DNA repair — •Thomas Höfer1, Martijn Luijsterburg2, Gesa von Bornstaedt1, and Roel van Driel3 — 1Deutsches Krebsforschungszentrum, Heidelberg, Germany — 2Karolinska Institute, Stockholm, Sweden — 3University of Amsterdam, The Netherlands
To understand how multi-protein complexes assemble and function on chromatin, we have combined quantitative analysis of a mammalian DNA repair machinery in living cells with mathematical modeling. We found that the individual components exchange rapidly at the repair sites whereas their net accumulation evolved on a much slower timescale. Based on the experimental data, we developed a predictive kinetic model of how multi-protein repair complexes assemble. Complex formation is orchestrated by progressive enzymatic modifications of the chromatin substrate, leaving considerable freedom for the binding mode of individual proteins. We demonstrate that the faithful recognition of DNA lesions is a time-consuming process, while subsequently repair complexes form rapidly through random and reversible assembly. Our analysis reveals a fundamental conflict between specificity and efficiency of chromatin-associated protein machineries and shows how a trade-off is negotiated through reversibility of protein binding.