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Visualization of eukaryotic DNA mismatch repair reveals distinct recognition and repair intermediates.

Cell | Nov 23, 2011

DNA mismatch repair (MMR) increases replication fidelity by eliminating mispaired bases resulting from replication errors. In Saccharomyces cerevisiae, mispairs are primarily detected by the Msh2-Msh6 complex and corrected following recruitment of the Mlh1-Pms1 complex. Here, we visualized functional fluorescent versions of Msh2-Msh6 and Mlh1-Pms1 in living cells. We found that the Msh2-Msh6 complex is an S phase component of replication centers independent of mispaired bases; this localized pool accounted for 10%-15% of MMR in wild-type cells but was essential for MMR in the absence of Exo1. Unexpectedly, Mlh1-Pms1 formed nuclear foci that, although dependent on Msh2-Msh6 for formation, rarely colocalized with Msh2-Msh6 replication-associated foci. Mlh1-Pms1 foci increased when the number of mispaired bases was increased; in contrast, Msh2-Msh6 foci were unaffected. These findings suggest the presence of replication machinery-coupled and -independent pathways for mispair recognition by Msh2-Msh6, which direct formation of superstoichiometric Mlh1-Pms1 foci that represent sites of active MMR.

Pubmed ID: 22118461 RIS Download

Mesh terms: Animals | DNA Mismatch Repair | DNA Repair Enzymes | DNA Replication | DNA-Binding Proteins | Exodeoxyribonucleases | Humans | MutS Homolog 2 Protein | Proliferating Cell Nuclear Antigen | Saccharomyces cerevisiae

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Associated grants

  • Agency: NIGMS NIH HHS, Id: R01 GM074215
  • Agency: NIGMS NIH HHS, Id: R01 GM074215-08
  • Agency: NIGMS NIH HHS, Id: GM085764
  • Agency: NCI NIH HHS, Id: P30 CA023100-27
  • Agency: NCI NIH HHS, Id: P30 CA023100
  • Agency: NCI NIH HHS, Id: CA23100
  • Agency: NIGMS NIH HHS, Id: GM074215
  • Agency: NIGMS NIH HHS, Id: R01 GM050006-24
  • Agency: NIGMS NIH HHS, Id: P50 GM085764
  • Agency: NIGMS NIH HHS, Id: GM50006
  • Agency: NIGMS NIH HHS, Id: R01 GM050006

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