Mechanisms in Site-Specific Recombination
Site-specific recombination is involved in regulation of gene expression, differentiation, evolution, and the life cycle of several viral genomes. As a model system for the molecular mechanisms of this genetic transaction, we are studying the integration/excision reaction of bacteriophage lambda. Among the questions being explored are those pertaining to the directionality of recombination, the mechanisms by which DNA strands are cut, exchanged and resealed, the identification of DNA target sites in a sea of "incorrect" DNA sequences, and the regulation of recombination.
Global Regulation of Cell Physiology
In the regulation and/or monitoring of overall cell physiology, a small number of proteins can affect the expression of a large number of apparently unrelated genes, some being turned on and others being turned off by the same protein. Several of these global regulatory proteins induce sharp bends in DNA at their site of binding. Our recent work has led to consideration of how these global regulatory proteins work.
DNA replication, protein synthesis, nucleosome organization, and recombination all depend upon the assembly of protein-DNA complexes. We are studying the rules and mechanisms governing the structure and function of these multicomponent higher-order complexes.