Research Interests

Peter von Hippel and his associates are using physical biochemical approaches to study what might be called the molecular basis of gene expression. Most of their experimental work is now concerned with the function and regulation of the complexes that control DNA transcription and replication with studies focused primarily on transcription with the E. coli DNA-dependent RNA polymerase and its regulatory factors and on replication with the seven-protein bacteriophage T4-coded DNA replication system. Comparative studies are also underway using selected components of some equivalent eukaryotic systems. In transcription the von Hippel lab is studying the transcription cycle, both at the overall operon level and at the level of the various steps of the single-nucleotide addition-excision cycle. At the operon level they are studying regulatory interactions that control activation and repression at initiation, the kinetics of elongation, and the molecular bases of the elongation-termination decision at both intrinsic and rho-dependent transcription terminators, together with the mechanisms of antiterminators. At the single-nucleotide addition-excision cycle level they are using various kinetic techniques to understand the molecular origins of transcriptional processivity and fidelity. In replication the work of the group began with the studies of the cooperative binding of the T4 gene 32 (single-stranded DNA binding) protein to the single-stranded DNA (and RNA). This led the group to examine the interactions of the other components of the system, including those of the DNA polymerase with the primer-template and the polymerase accessory proteins. These studies have shown that the basically non-processive T4 DNA polymerase can be rendered fully processive by means of an accessory protein processivity factor and that the role of the other accessory proteins is to carry out specific and ATP-dependent "loading" of the processivity factor onto the polymerase at the primer-template junction within the replication fork. These interactions produce the five-protein holoenzyme complex that can carry out leading strand DNA replication with essentially in vitro rate, fidelity, and processivity. The helicase of the T4 DNA replication system functions as a hexamer and can engage in ATPase-driven translocation unidirectionally along single-stranded DNA. The structure of the helicase-primase sub-assembly is also currently being examined, as is the mode of assembly of these components into a fully functional and coupled DNA replication system. In all these studies the elucidation of the detailed mechanisms and general principles of protein-nucleic acid and protein-protein interactions that underlie the function of these biologically central complexes is emphasized.

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Primary Section

Section 21: Biochemistry

Secondary Section

Section 29: Biophysics and Computational Biology