MutT protein specifically hydrolyses a potent mutagenic substrate for DNA synthesis.
Errors in the replication of DNA are a major source of spontaneous mutations, and a number of cellular functions are involved in correction of these errors to keep the frequency of spontaneous mutations very low. We report here a novel mechanism which prevents replicational errors by degrading a potent mutagenic substrate for DNA synthesis. This error-avoiding process is catalysed by a protein encoded by the mutT gene of Escherichia coli, mutations of which increase the occurrence of A.T----C.G transversions 100 to 10,000 times the level of the wild type. Spontaneous oxidation of dGTP forms 8-oxo-7,8-dihydro-2'-dGTP (8-oxodGTP), which is inserted opposite dA and dC residues of template DNA with almost equal efficiency, and the MutT protein specifically degrades 8-oxodGTP to the monophosphate. This indicates that elimination from the nucleotide pool of the oxidized form of guanine nucleotide is important for the high fidelity of DNA synthesis.
Maki
H
H
Department of Biochemistry, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Sekiguchi
M
M
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001482:Base Composition; D001483:Base Sequence; D004261:DNA Replication; D003838:Deoxyadenine Nucleotides / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D029968:Escherichia coli Proteins; D006868:Hydrolysis; D007700:Kinetics; D008969:Molecular Sequence Data; D009154:Mutation; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D011755:Pyrophosphatases; D013379:Substrate Specificity; D013698:Templates, Genetic
D001426:Bacterial Proteins; D003838:Deoxyadenine Nucleotides; D029968:Escherichia coli Proteins; D010744:Phosphoric Monoester Hydrolases; D011755:Pyrophosphatases; C052211:mutT protein, E coli; C026600:2'-deoxyadenosine triphosphate