A Drosophila ribosomal protein contains 8-oxoguanine and abasic site DNA repair activities.
Ionizing radiation and normal cellular respiration form reactive oxygen species that damage DNA and contribute to a variety of human disorders including tumor promotion and carcinogenesis. A major product of free radical DNA damage is the formation of 8-oxoguanine, which is a highly mutagenic base modification produced by oxidative stress. Here, Drosophila ribosomal protein S3 is shown to cleave DNA containing 8-oxoguanine residues efficiently, The ribosomal protein also contains an associated apurinic/apyrimidinic (AP) lyase activity, cleaving phosphodiester bonds via a beta,delta elimination reaction. The significance of this DNA repair activity acting on 8-oxoguanine is shown by the ability of S3 to rescue the H2O2 sensitivity of an Escherichia coli mutM strain (defective for the repair of 8-oxoguanine) and to abolish completely the mutator phenotype of mutM caused by 8-oxoguanine-mediated G-->T transversions. The ribosomal protein is also able to rescue the alkylation sensitivity of an E.coli mutant deficient for the AP endonuclease activities associated with exonuclease III (xth) and endonuclease IV (nfo), indicating for the first time that an AP lyase can represent a significant source of DNA repair activity for the repair of AP sites. These results raise the possibility that DNA repair may be associated with protein translation.
Yacoub
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A
Department of Biochemistry, Louisiana State University, Baton Rouge, LA 70803, USA.
Augeri
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L
Kelley
M R
MR
Doetsch
P W
PW
Deutsch
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WA
D000818:Animals; D001483:Base Sequence; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D043382:DNA-Formamidopyrimidine Glycosylase; D043223:Deoxyribonuclease IV (Phage T4-Induced); D004330:Drosophila / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics; D029968:Escherichia coli Proteins; D005816:Genetic Complementation Test; D005982:Glutathione Transferase / Q000235:genetics; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D008190:Lyases / Q000378:metabolism; D008969:Molecular Sequence Data; D009699:N-Glycosyl Hydrolases / Q000235:genetics; D009838:Oligodeoxyribonucleotides; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism*
D029968:Escherichia coli Proteins; D009838:Oligodeoxyribonucleotides; D012269:Ribosomal Proteins; C044152:ribosomal protein S3; C024829:8-hydroxyguanine; D006147:Guanine; D005982:Glutathione Transferase; D043223:Deoxyribonuclease IV (Phage T4-Induced); C468972:endonuclease IV, E coli; D009699:N-Glycosyl Hydrolases; D043382:DNA-Formamidopyrimidine Glycosylase; C468610:DNA-formamidopyrimidine glycosylase, E coli; D008190:Lyases; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase