Efficient DNA base excision repair in ataxia telangiectasia cells

Ataxia telangiectasia (A-T) cells are sensitive to a broad range of free-ra dical-producing and alkylating agents. Damage caused by such agents is in p art repaired by base excision [base excision repair (BER)]. Two BER pathway s 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 ex posed to ionizing radiation and radiomimetic agents, more recent experiment s performed in non-dividing A-T cells and the demonstrated interaction of t he 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 m utation involved was homozygous and completely inactivated the ATM protein. No difference was observed between affected individuals and heterozygous o r homozygous wild-type relatives in their capacity to perform DNA repair by either one-nucleotide insertion or the long-patch pathway. Hence, the puta tive DNA-repair defect in A-T cells, if any, does not involve BER.