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PMS2 endonuclease activity has distinct biological functions and is essential for genome maintenance.

The DNA mismatch repair protein PMS2 was recently found to encode a novel endonuclease activity. To determine the biological functions of this activity in mammals, we generated endonuclease-deficient Pms2E702K knock-in mice. Pms2EK/EK mice displayed increased genomic mutation rates and a strong cancer predisposition. In addition, class switch recombination, but not somatic hypermutation, was impaired in Pms2EK/EK B cells, indicating a specific role in Ig diversity. In contrast to Pms2-/- mice, Pms2EK/EK male mice were fertile, indicating that this activity is dispensable in spermatogenesis. Therefore, the PMS2 endonuclease activity has distinct biological functions and is essential for genome maintenance and tumor suppression.

Pubmed ID: 20624957 RIS Download

Mesh terms: Adenosine Triphosphatases | Animals | Cells, Cultured | DNA Mismatch Repair | DNA Repair Enzymes | DNA-Binding Proteins | Embryo, Mammalian | Endonucleases | Female | Fertility | Fibroblasts | Genetic Predisposition to Disease | Genomic Instability | Genotype | Humans | Immunoglobulin Class Switching | Immunoglobulin G | Lymphoma | Male | Mice | Mice, Knockout | Mismatch Repair Endonuclease PMS2 | Mutation | Reverse Transcriptase Polymerase Chain Reaction

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Associated grants

  • Agency: NIGMS NIH HHS, Id: GM45190
  • Agency: NCI NIH HHS, Id: R01 CA093484
  • Agency: NCI NIH HHS, Id: R01 CA076329
  • Agency: NCI NIH HHS, Id: R01 CA102705
  • Agency: Howard Hughes Medical Institute, Id: CA102705
  • Agency: NCI NIH HHS, Id: R01 CA072649
  • Agency: NCI NIH HHS, Id: CA93484
  • Agency: NCI NIH HHS, Id: CA72649
  • Agency: NCI NIH HHS, Id: CA76329
  • Agency: NCI NIH HHS, Id: R01 GM045190
  • Agency: NIGMS NIH HHS, Id:

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