Streptomyces coelicolor Encodes a Urate-Responsive Transcriptional Regulator with Homology to PecS from Plant Pathogens

Many transcriptional regulators control gene activity by responding to specific ligands. Members of the multiple-antibiotic resistance regulator (MarR) family of transcriptional regulators feature prominently in this regard, and they frequently function as repressors in the absence of their cognate ligands. Plant pathogens such as Dickeya dadantii encode a MarR homolog named PecS that controls expression of a gene encoding the efflux pump PecM in addition to other virulence genes. We report here that the soil bacterium Streptomyces coelicolor also encodes a PecS homolog (SCO2647) that regulates a pecM gene (SCO2646). S. coelicolor PecS, which exists as a homodimer, binds the intergenic region between pecS and pecM genes with high affinity. Several potential PecS binding sites were found in this intergenic region. The binding of PecS to its target DNA can be efficiently attenuated by the ligand urate, which also quenches the intrinsic fluorescence of PecS, indicating a direct interaction between urate and PecS. In vivo measurement of gene expression showed that activity of pecS and pecM genes is significantly elevated after exposure of S. coelicolor cultures to urate. These results indicate that S. coelicolor PecS responds to the ligand urate by attenuated DNA binding in vitro and upregulation of gene activity in vivo. Since production of urate is associated with generation of reactive oxygen species by xanthine dehydrogenase, we propose that PecS functions under conditions of oxidative stress

N-Acetyltransferase polymorphism and human cancer risk

Because of the important role ofN-acetyltransferase (NAT) enzymes in both metabolic activation and detoxification of certain precarcinogens, such as homo-and heterocyclic arylamines, extensive research in the past has focused on the relationship between the distribution of different variants of these enzymes and cancer susceptibility. In this context, we examined the relationship between the acetylator type of two NAT isozymes (NAT1 and NAT2) and cancer risk. It was shown that any independent overall association of those diseases with acetylation for eitherNATl orNAT2 is likely to be weak at most. Besides individual genetic profile, differences in the degree of exposure to environmental precarcinogens should also be considered. It was suggested that smoking and red meat intake were associated with bothNATl andNAT2 genotype in the carcinogenesis. A gene-gene interaction, even linkage betweenNATl andNAT2 may also exist