Removal of O6-methylguanine from DNA of normal and xeroderma pigmentosum-derived lymphoblastoid lines

Abstract

The ability to excise (repair) UV-induced pyrimidine dimers in Escherichia coli is not related to its ability to remove N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced O6-methylguanine (O6-MeG) from DNA. It was therefore surprising that certain xeroderma pigmentosum cell lines, deficient in dimer excision, were also unable to remove O6-MeG. We find that removal of O6-MeG occurs rapidly with a half life of less than 1 h. Two cell types can be distinguished: mex+, which remove O6-MeG residues produced by incubation with 0.5 microgram ml-1 MNNG, and mex- cells, which are unable to remove the adduct. Xeroderma pigmentosum-derived lymphoblastoid lines of complementation groups A, C or D may be either mex+ or mex-. The biochemical mechanism for the removal of O6-MeG in human cells is distinct from the excision of adducts produced by compounds such as N-acetoxy-N-2-acetylaminofluorene (AAAF) or by UV irradiation but it is not clear whether the distinction between mex+ and mex- lines is genetic or epigenetic.