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J Biol Chem. 2013 Nov 15;288(46):32952-62. doi: 10.1074/jbc.M113.507772. Epub 2013 Oct 4.

Search for proteins required for accurate gene expression under oxidative stress: roles of guanylate kinase and RNA polymerase.

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  • 1From the Frontier Research Center and Department of Biochemistry, Fukuoka Dental College, Fukuoka 814-0193 and.


In aerobically growing cells, in which reactive oxygen species are produced, the guanine base is oxidized to 8-oxo-7,8-dihydroguanine, which can pair with adenine as well as cytosine. This mispairing causes alterations in gene expression, and cells possess mechanisms to prevent such outcomes. In Escherichia coli, 8-oxo-7,8-dihydroguanine-related phenotypic suppression of lacZ amber is enhanced by mutations in genes related to the prevention of abnormal protein synthesis under oxidative stress. A genome-wide search for the genes responsible, followed by DNA sequence determination, revealed that specific amino acid changes in guanylate kinase and in the β and β' subunits of RNA polymerase cause elevated levels of phenotypic suppression, specifically under aerobic conditions. The involvement of the DnaB, DnaN, and MsbA proteins, which are involved in DNA replication and in preserving the membrane structure, was also noted. Interactions of these proteins with each other and also with other molecules may be important for preventing errors in gene expression.


Gene Expression; Guanylate Kinase; Oxidative Stress; Protein Synthesis; RNA Polymerase; RNA Synthesis

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