An end for mismatch repair

Abstract

DNA mismatch repair (MMR) is an important postreplicative repair mechanism that removes DNA polymerization errors and is responsible for increasing the fidelity of genome replication by orders of magnitude. Defects in MMR lead to the most common form of hereditary colon cancer and a variety of sporadic cancers (1–3). One of the main features of MMR is its ability to distinguish old and new DNA strands, but when a mismatch is found, how does MMR determine which sequence is the correct one? One of the first papers to describe MMR suggested that the MMR repair complex could have a special relationship with the replication apparatus (4), and that idea seems to be a central feature of strand discrimination in eukaryotes. In a study published in PNAS, Nick McElhinny et al. (5) provide evidence that the close relationship between MMR and replication leads to preferential repair of mismatches near initiation sites for DNA synthesis.