Functional cooperation of MutT, MutM and MutY proteins in preventing mutations caused by spontaneous oxidation of guanine nucleotide in Escherichia coli.
8-Oxo-dGTP (8-oxo-7,8-dihydrodeoxyguanosine triphosphate) is a potent mutagenic substrate for DNA synthesis. The accumulation of 8-oxo-dGTP in the nucleotide pool induces G:C-->T:A transversion as well as A:T-->C:G transversion, and Escherichia coli cells possess mechanisms for preventing such mutations. The mutT gene product specifically hydrolyzes 8-oxo-dGTP to the monophosphate form while the mutM and the mutY gene products function to correct mispairs caused by incorporation of 8-oxoguanine into DNA. From analyses of forward mutations induced in cells lacking 8-oxo-dGTPase (MutT protein) and/or repair enzymes that suppress mutations caused by 8-oxoguanine in DNA (MutM and MutY proteins), cooperative functions of these proteins in control of the spontaneous mutagenesis became evident. In mutator strains lacking MutT and/or MutM proteins, 8-oxoguanine of DNA increased to a concentration expected from the increased rate of mutation.
Tajiri
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T
Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Maki
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Sekiguchi
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D000080242:8-Hydroxy-2'-Deoxyguanosine; D001426:Bacterial Proteins / Q000502:physiology*; D001483:Base Sequence; D045647:DNA Glycosylases; D004260:DNA Repair / Q000235:genetics / Q000502:physiology*; D004269:DNA, Bacterial / Q000378:metabolism; D043382:DNA-Formamidopyrimidine Glycosylase; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D029968:Escherichia coli Proteins; D005798:Genes, Bacterial; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D006150:Guanine Nucleotides / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D008969:Molecular Sequence Data; D009699:N-Glycosyl Hydrolases / Q000502:physiology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000235:genetics*; D010744:Phosphoric Monoester Hydrolases / Q000502:physiology; D017354:Point Mutation; D011755:Pyrophosphatases; D013489:Suppression, Genetic; D013698:Templates, Genetic
D001426:Bacterial Proteins; D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; D006150:Guanine Nucleotides; C024829:8-hydroxyguanine; D006147:Guanine; D006160:Guanosine Triphosphate; D000080242:8-Hydroxy-2'-Deoxyguanosine; D010744:Phosphoric Monoester Hydrolases; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; C061738:mutY adenine glycosylase; D043382:DNA-Formamidopyrimidine Glycosylase; C468610:DNA-formamidopyrimidine glycosylase, E coli; D011755:Pyrophosphatases; C052211:mutT protein, E coli; D003849:Deoxyguanosine