Endonucleolytic Function of MutLα in Human Mismatch Repair

  title={Endonucleolytic Function of MutLα in Human Mismatch Repair},
  author={Farid A Kadyrov and Leonid Dzantiev and Nicoleta Constantin and Paul Modrich},
Half of hereditary nonpolyposis colon cancer kindreds harbor mutations that inactivate MutLa (MLH1 PMS2 heterodimer). MutLa is required for mismatch repair, but its function in this process is unclear. We show that human MutLa is a latent endonuclease that is activated in a mismatch-, MutSa-, RFC-, PCNA-, and ATP-dependent manner. Incision of a nicked mismatch-containing DNA heteroduplex by this four-protein system is strongly biased to the nicked strand. A mismatch-containing DNA segment… CONTINUE READING
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