- Dr. McHenry studies the enzymology of DNA replication with primary focus on the E. coli replicase. Because of the conserved nature of replication mechanisms, many central principles, applicable to all life forms, have been established in this system. The low GC Gram-positive bacteria diverged from E. coli approximately two billion years ago. This provides an opportunity to learn how the central themes of DNA replication vary in highly divergent organisms. The McHenry lab has established a full in vitro system that requires 13 purified proteins. Current focus is upon learning how two distinct replicases coordinate their activities during lagging strand replication. A third program focuses upon the chemical biology of DNA replication—the discovery and development of small molecules that block each of the steps of the complex replication process. These compounds will provide tools that aid biochemical studies and for blocking specific steps in vivo for cell physiology studies.