MISMATCH REPAIR CO-OPTED BY HYPERMUTATION

Mice homozygous for a disrupted allele of the mismatch repair gene Pms 2 have a mutator phenotype. When this allele is crossed into quasi-mon oclonal (QM) mice, which have a very limited B cell repertoire, homozy gotes have fewer somatic mutations at the immunoglobulin heavy chain a cid lambda chain loci than do heterozygotes or wild-type QM mice, That is, mismatch repair seems to contribute to somatic hypermutation rath er than stifling it. It is suggested that at immunoglobulin loci in hy permutable B cells, mismatched base pairs are ''corrected'' according to the newly synthesized DNA strand, thereby fixing incipient mutation s instead of eliminating them.