A DROSOPHILA RIBOSOMAL-PROTEIN CONTAINS 8-OXOGUANINE AND ABASIC SITE DNA-REPAIR ACTIVITIES

Ionizing radiation and normal cellular respiration form reactive oxyge n species that damage DNA and contribute to a variety of human disorde rs including tumor promotion and carcinogenesis. A major product of fr ee radical DNA damage is the formation of 8-oxoguanine, which is a hig hly mutagenic base modification produced by oxidative stress. Here, Dr osophila ribosomal protein S3 is shown to cleave DNA containing 8-oxog uanine residues efficiently. The ribosomal protein also contains an as sociated apurinic/apyrimidinic (AP) lyase activity, cleaving phosphodi ester bonds via a beta,delta elimination reaction. The significance of this DNA repair activity acting on 8-oxoguanine is shown by the abili ty of S3 to rescue the H2O2 sensitivity of an Escherichia coli mutM st rain (defective for the repair of 8-oxoguanine) and to abolish complet ely the mutator phenotype of mutM caused by 8-oxoguanine-mediated G--> T transversions. The ribosomal protein is also able to rescue the alky lation sensitivity of an E.coli mutant deficient for the AP endonuclea se activities associated with exonuclease III (xth) and endonuclease I V (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 associate d with protein translation.