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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

Authors

  • van Oers JM
  • Roa S
  • Werling U
  • Liu Y
  • Genschel J
  • Hou H
  • Sellers RS
  • Modrich P
  • Scharff MD
  • Edelmann W

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Data

July 27, 2010

Associated Grants

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

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
  • Mutation
  • Reverse Transcriptase Polymerase Chain Reaction