MISMATCH BINDING-PROTEINS AND TOLERANCE TO ALKYLATING-AGENTS IN HUMAN-CELLS

The Mex- (Mer-) phenotype of human cells is characterised by a sensitivity to agents such as N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) and N-methyl-N-nitrosourea (MNU). The hypersensivity of Mex- cells is a consequence of their failure to express the DNA-repair enzyme m6-Gua-DNA methyltransferase. Resistance to MNNG and MNU may be acquired by Mex- cells either by reexpression of a methyltransferase function or by an ill-defined process of tolerance in which the cytotoxic potential of m6-Gua is circumvented without the altered base being removed from DNA. It has been suggested that tolerance might involve an altered mismatch correcting function. We have investigated proteins which recognise and bind specifically to DNA fragments containing single-base mismatches. Cell-free extracts of a Burkitt's lymphoma cell line (Raji) contain two such mismatch binding activities. Neither protein appears to have a high affinity for m6-Gua-containing base pairs. The data indicate that m6-Gua-containing base pairs might be poor substrates for mismatch repair processes in human cells. © 1990.