All Good Things Must Bend: the Energetics of DNA Shape and Flexibility in Biological Assemblies
Seminar Room 1, Newton Institute
DNA-loop formation is an essential mechanistic aspect of many biological processes including gene regulation, DNA replication, and recombination. These loops are mediated by proteins bound at specific sites along the contour of a single DNA molecule and are closely coupled to the topological state of DNA domains through supercoiling, knotting, and linking. The complex interplay between DNA topology and the regulation of DNA transactions remains poorly understood and the effects of a chromatin environment on such interactions are essentially unknown. However, new insights can come from novel experimental approaches and computational models of DNA flexibility and folding under geometric and/or topological constraints. Experimental studies of Cre-loxP recombination and lac-repressor-mediated gene regulation will be used to illustrate the problems and general principles of complex nucleoprotein organization. A new method for directly computing the thermodynamic (i.e., free-energy) cost for mesoscopic models of nucleoprotein assemblies will also be discussed.