Gene expression in normal and pathological conditions is mediated by RNA polymerase enzymes, a family of complex, multisubunit molecular machines that is highly conserved in evolution. RNA polymerase function is controlled not only at the level of access to genes (transcription initiation), but also during enzyme progression as RNAP carries out its sequential readout of the gene message. An important example of such control occurs in HIV virus and is mediated by its major regulator, the TAT gene. The central models for understanding enzymatic mechanisms involved in transcriptional regulation are the antitermination proteins of the E. coli bacteriophage lambda, the Q protein, which modifies RNA polymerase near its initiation site, but then becomes a subunit of the enzyme, allowing it to elongate more efficiently and to progress through transcription termination signals. The investigator will study important elements of both the Q polypeptide and the subunits of RNA polymerase that are required for their physical and functional interaction, particularly the sigma initiation factor which mediates the initial engagement of Q protein with RNA polymerase, and he will examine the altered enzymatic properties of Q modified RNA polymerase. He will investigate the mechanism of transcription termination and the manner in which regulatory proteins interfere with this process.
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