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	2006 Fellow			Rodrigo Galhardo, Ph.D. Laboratory of Susan M. Rosenberg, Ph.D. Dept. of Molecular and Human Genetics Baylor College of Medicine One Baylor Plaza, S809A Mail Stop BCM225 Houston, TX 77030-3411 Phone: (713) 798-6924 Fax: (713) 798-8967 Email: galhardo@bcm.edu

Country: BRAZIL

Field: Genetics/Molecular Mechanisms of Mutagenesis and Genetic

Research Interest: Mechanism and regulation of DinB-dependent stationary-phase mutagenesis in Escherichia coli. Genetic stability and mutation rates are tightly regulated features of all living organisms. The understating of how cells manage such rates has many implications for important themes in modern biology, such as cancer onset, aging, and acquisition of drug resistance by pathogens. Stress-induced or stationary-phase mutagenesis is a well-documented phenomenon occurring in starved bacterial cells. In an Escherichia coli model assay system, when starved for long periods, a subset of the bacterial population acquires a hypermutable state, as part of a regulated stress response. The resulting mutagenesis requires the general stress response regulator RpoS and the induction of the SOS DNA-damage response. A pivotal role is exerted by the DinB protein also known as pol IV. DinB is a member of the Y family of DNA polymerases. DinB, an error-prone DNA polymerase, is responsible for the vast majority of stress-induced point mutations arising in these starved cells. Transcriptional regulation of DinB in the stationary phase might be important for the proper acquisition of the hypermutable state, but other factors might also regulate DinB enzymatic activity in growth-arrested cells. The primary aim of our project is to understand the activation of DinB in stationary-phase mutagenesis, by means of a genetic screen designed to identify regulatory mutants of dinB and possibly other DNA replication components. We expect that important clues to DinB function and regulation will be identified in these experiments, which may also be relevant for the DinB homologues present in eukaryotic cells.