Metal ions figure significantly in the activity of many enzymes biological systems also make very subtle distinctions among metallic elements to control fundamental information transduction processes. Moreover, proteins with active-site sulfhydryl groups (potential metal binding targets) play key roles in DNA replication and repair. Presently, our understanding of what determines specific protein-metal interactions and of how alternative metals can modulate protein behavior is incomplete. Summers studies the bacterial mercury (Hg) resistance (mer) locus, an operon controlled by a small, Hg-responsive, DNA binding, transcriptional activator/repressor, MerR. Her work has focussed on MerR interactions with its cognate DNA site, merOP, and with RNA polymerase. She will use molecular genetics and biochemistry to discern the MerR domains which enable it to sequester RNA polymerase at merOP prior to induction and those responsible for the DNA distortion which takes place during activation. She will dissect the relationship between the mer operon and the chromosomally encoded oxidative shock regulon. Finally, she will employ random and site specific mutagenesis to obtain MerR mutants responsive to transition metals other than Hg(II). These variant MerR proteins will be examined in vitro for their metal and DNA binding properties. %%% Certain micro-organisms have the ability to grow in the presence of chemicals which are toxic to most other organisms. One way this is accomplished is through conversion of the toxic form of the chemical to a non or less toxic form. This proposal investigates the genetic mechanisms which regulate and control the expression of a set of genes in bacteria which function in the detoxification of mercury. $$$//
