Molecular switch control of nucleic-acid processing machines*

Single-molecule techniques have revolutionized our understanding of the mechanics and dynamics of DNA and of the molecular machines that process it. In this talk, I will discuss our work developing new single-molecule methods and integrating them with computational approaches to provide unprecedented access into the mechanisms of these molecular machines. I will discuss various applications of these approaches, in particular our measurements of helicases, which use the energy of ATP hydrolysis to separate the strands of nucleic acid duplexes and are essential components of the cellular machinery that maintains and repairs the genome. Our work shows how prototype members of helicases process DNA and possess molecular switches that regulate their activity. Interactions with protein partners are likely to provide control over these switches and thus the roles the helicases play. Our findings provide new insights on the mechanisms by which these molecular machines function and are regulated in the cell.