Mismatch repair proteins as sensors of alkylation DNA damage

The DNA mismatch repair (MMR) system maintains genome integrity by correcting replication errors. MMR also stimulates checkpoint and cell death responses to DNA damage suggested by the resistance of MMR-defective tumor cells to several chemotherapeutic agents. MMR-dependent cytotoxic response may result from futile repair; however, MMR-mediated apoptosis has been genetically separated from its repair function. In a recent issue of Molecular Cell, Yoshioka and coworkers show that MMR complexes (MutSα and MutLα) are required for the recruitment of ATR-ATRIP to sites of alkylation damage, demonstrating that MMR complexes can function as sensors in DNA damage signal transduction.