Regulation and Structure of the mer Operon

金属离子在许多酶的活性中起重要作用 生物系统也会在 控制基本信息传导的金属元素 流程. 此外，具有活性位点巯基的蛋白质 （潜在的金属结合靶点）在DNA复制中起关键作用 和修复。 目前，我们对是什么决定了 特定的蛋白质-金属相互作用以及替代金属 调节蛋白质行为的机制是不完整的。 萨默斯研究了 细菌汞（Hg）抗性（mer）位点，一个操纵子控制的 通过一个小的，汞反应，DNA结合，转录 激活子/阻遏子，MerR。 她的工作集中在MerR 与其同源DNA位点merOP以及与RNA的相互作用 聚合酶。 她将利用分子遗传学和生物化学， 识别MerR结构域，使其能够隔离RNA 诱导前merOP的聚合酶和那些负责 在激活过程中发生的DNA扭曲。 她将 剖析mer操纵子与 染色体编码的氧化休克调节子。 最后，她会 采用随机和位点特异性诱变获得MerR突变体 对除Hg（II）以外的过渡金属敏感。 这些变体 将在体外检查MerR蛋白的金属和DNA 结合性能 %%% 某些微生物有能力在存在 对大多数其他生物体有毒的化学物质。 一种方法是 完成是通过转换的有毒形式的 化学物质转化为无毒或毒性较小的形式。 该提案调查了 调节和控制基因表达的遗传机制 细菌中的一组基因， 汞 $$$//

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. $$$//