Suppression of human DNA alkylation-repair defects by Escherichia coli DNA-repair genes.
The ada-alkB operon protects Escherichia coli against the effects of many alkylating agents. We have subcloned it into the pSV2 mammalian expression vector to yield pSV2ada-alkB, and this plasmid has been introduced into Mer- HeLa S3 cells, which are extremely sensitive to killing and induction of sister chromatid exchange by alkylating agents. One transformant (the S3-9 cell line) has several integrated copies of pSV2ada-alkB and was found to express a very high level of the ada gene product, the 39-kDa O6-methylguanine-DNA methyltransferase. S3-9 cells were found to have become resistant to killing and induction of sister chromatid exchange by two alkylating agents, N-methyl-N'-nitro-N-nitrosoguanidine and N,N'-bis(2-chloroethyl)-N-nitro-sourea. This shows that bacterial DNA alkylation-repair genes are able to suppress the alkylation-repair defects in human Mer- cells.
D000477:Alkylating Agents / Q000633:toxicity*; D000478:Alkylation; D003001:Cloning, Molecular; D004260:DNA Repair; D004351:Drug Resistance; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D005822:Genetic Vectors; D006367:HeLa Cells; D006801:Humans; D008780:Methyltransferases / Q000235:genetics*; D019853:O(6)-Methylguanine-DNA Methyltransferase; D010641:Phenotype; D013045:Species Specificity; D013489:Suppression, Genetic
D000477:Alkylating Agents; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase