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PCNA and MutLα: Partners in crime in triplet repeat expansion?

Biosynthetic errors that escape the proofreading activity of DNA polymerases are processed by the mismatch repair (MMR) system. Their correction entails the degradation of the mismatch-containing section of the newly synthesized strand and its error-free resynthesis. Although the main MMR players have been identified, the key mechanistic details of the process remain obscure. One of these concerns strand discrimination. How is MMR targeted to the newly synthesized strand? In PNAS, Pluciennik et al. (1) help elucidate this phenomenon. Moreover, their findings suggest that MMR proteins might be involved in the metabolism of noncanonical structures that arise in nonreplicating DNA.