The applicants laboratory has recently identified five trans-acting regulatory factors governing prokaryotic gene expression in response to changes in oxygen tension and light intensity. During the proposed funding period, each of these regulatory factors will be genetically and biochemically characterized for their role in controlling gene expression in response to oxygen and light. Two """"""""oxygen responding"""""""" regulatory proteins are additional members of a family of two-component response regulators which indicates that one regulatory protein is a membrane spanning sensor kinase that transmits information about anaerobioses via phosphorylation of a DNA binding response regulator. An additional sensor kinase is described which is thought to be involved in sensing light intensity by monitoring the redox state of the electron transport chain. This additional redox responding regulator is structurally similar to a protein in mitochondria which is known to be involved in expression of cytochrome oxidase; a protein implicated in degenerative diseases such as Parkinson's and Ischemic heart disease. The laboratory is also characterizing a light sensing regulatory protein involved in controlling expression of the enzyme S-adenosyl homocysteine hydrolase (SAHase). SAHase is an important contributing factor in the cytotoxic effects of adenosine leading to severe immune deficiency in patents with adenosine deaminase (ADA) deficiency.
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