Selective binding to DNA base pair mismatches by proteins from human cells

Using the technique of delayed oligonucleotide migration through polyacrylamide gels, we have demonstrated that cell-free extracts of the human Burkitt's lymphoma cell line Raji contain proteins which can recognize and bind to mismatched single base pairs in short fragments of DNA. One of these binding proteins resembles an activity previously reported in HeLa cells (Jiricny, J., Hughes, M., Corman, N., and Rudkin, B. B. (1988) Proc. Natl. Acad. Sci. U. S. A. 85, 8860-8864) and recognizes DNA containing G.T mismatches. Extracts of Raji cells contain an additional activity which recognizes A.C, T.C, or T.T mismatches in DNA. This second binding protein can be distinguished from the G.T binding activity by its size, substrate specificity, and its fractionation properties. In addition to Raji cells, the new mismatch binding protein is present in extracts of human lymphoblastoid cell lines from a normal individual and a xeroderma pigmentosum patient as well as the SV40-transformed human fibroblast cell line MRC5V1. It seems likely that this novel activity is involved in a broad specificity DNA repair pathway for the correction of single base mismatches in human cells.