“…It seems likely that reduction of the ATM protein even to the extent of 50% as predicted in A-T heterozygotes alters the response to ionizing radiation. While A-T heterozygotes do not exhibit any of the major symptoms of the disease, cells in culture have intermediate radiosensitivity between homozygotes and controls as determined by a series of di erent assays (Chen et al, 1978;Rudolph et al, 1989;Cole et al, 1988;Lavin et al, 1992;Rosin and Ochs, 1986;Sanford and Parshad, 1990;Scott et al, 1994;Shiloh et al, 1986). This intermediate radiosensitivity is most likely due to reduced ATM protein since the great majority of mutations in ATM are predicted to give rise to truncated proteins (Savitsky et al, 1995a;Gilad et al, 1996;Byrd et al, 1996;Telatar et al, 1996).…”