title: Efficient DNA base excision repair in ataxia telangiectasia cells.
abstract: Ataxia telangiectasia (A-T) cells are sensitive to a broad range of free-radical-producing and alkylating agents. Damage caused by such agents is in part repaired by base excision [base excision repair (BER)]. Two BER pathways have been demonstrated in mammalian cells: a single-nucleotide-insertion pathway and a long-patch pathway involving resynthesis of 2-10 nucleotides. Although early studies failed to detect DNA-repair defects in A-T cells exposed to ionizing radiation and radiomimetic agents, more recent experiments performed in non-dividing A-T cells and the demonstrated interaction of the A-T-mutated protein (ATM) with the BRCA1 gene product suggest that a DNA-repair defect may underlie, at least in part, the radiation sensitivity in A-T cells. We have analysed BER of a single abasic site or a single uracil in two A-T families, using an in vitro BER system. In both families, the mutation involved was homozygous and completely inactivated the ATM protein. No difference was observed between affected individuals and heterozygous or homozygous wild-type relatives in their capacity to perform DNA repair by either one-nucleotide insertion or the long-patch pathway. Hence, the putative DNA-repair defect in A-T cells, if any, does not involve BER.
authors.affiliation: DNA Repair Unit, Mutagenesis Laboratory, Istituto Nazionale Ricerca Cancro, Genova, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Cappelli
authors.forename: O
authors.initials: O
authors.lastname: Rossi
authors.forename: L
authors.initials: L
authors.lastname: Chessa
authors.forename: G
authors.initials: G
authors.lastname: Frosina
mesh_terms: D001260:Ataxia Telangiectasia / Q000235:genetics*; D002453:Cell Cycle; D002460:Cell Line; D004260:DNA Repair / Q000235:genetics*; D005091:Exons; D005260:Female; D017353:Gene Deletion; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007438:Introns; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D009154:Mutation; D010957:Plasmids / Q000378:metabolism