Our laboratory is concerned with the enzymology of eukaryotic DNA replication using as a model genome, the linear chromosome of herpes simplex Type I virus (HSV-1). We are also interested in the mechanism by which the virus establishes a latent infection in nerve cells. The HSV-1 genome, like cellular chromosomes, contains multiple, redundant, origins of replication. The 150 kilobase HSV-1 genome has been completely sequenced. Of the seventy-five genes in the genome, seven are essential for HSV-1 DNA replication. The proteins encoded by these seven genes have been purified and analyzed in detail. They include a DNA polymerase, a protein that enhances the processivity of deoxynucleotide polymerization by the polymerase, a single-strand DNA binding protein, a heterotrimeric enzyme with both DNA helicase and primase activities, and an origin binding protein that binds specifically to the HSV-1 origins of replication. A complex of these enzymes can promote the “rolling circle” replication of plasmeds containing a herpes virus origin of replication.

A long standing interest has been the enzymatic mechanism of homologous recombination. Our work in this area has led to the discovery of the isolation of the Ecoli Rec A protein which can promote strand exchange between DNA molecules which is the essence of homologous recombination.

Robert Lehman studied
the mechanism of DNA
replication in eukaryotes,
with most recent emphasis
on the replication of herpes
virus DNA and the neuronal
latency of herpes virus.