High-fidelity correction of genomic uracil by human mismatch repair activities

摘要

BackgroundDeamination of cytosine to produce uracil is a common and potentially mutagenic lesion in genomic DNA. U•G mismatches occur spontaneously throughout the genome, where they are repaired by factors associated with the base excision repair pathway. U•G mismatches are also the initiating lesion in immunoglobulin gene diversification, where they undergo mutagenic processing by redundant pathways, one dependent upon uracil excision and the other upon mismatch recognition by MutSα. While UNG is well known to initiate repair of uracil in DNA, the ability of MutSα to direct correction of this base has not been directly demonstrated.