1. PMS2 endonuclease activity has distinct biological functions and is essential for genome maintenance.
- Author
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van Oers JM, Roa S, Werling U, Liu Y, Genschel J, Hou H Jr, Sellers RS, Modrich P, Scharff MD, and Edelmann W
- Subjects
- Adenosine Triphosphatases genetics, Animals, Cells, Cultured, DNA Mismatch Repair genetics, DNA Repair Enzymes genetics, DNA-Binding Proteins genetics, Embryo, Mammalian cytology, Endonucleases genetics, Female, Fertility genetics, Fibroblasts cytology, Fibroblasts metabolism, Genetic Predisposition to Disease genetics, Genotype, Humans, Immunoglobulin Class Switching genetics, Immunoglobulin G genetics, Lymphoma genetics, Male, Mice, Mice, Knockout, Mismatch Repair Endonuclease PMS2, Mutation, Reverse Transcriptase Polymerase Chain Reaction, Adenosine Triphosphatases metabolism, DNA Repair Enzymes metabolism, DNA-Binding Proteins metabolism, Endonucleases metabolism, Genomic Instability
- Abstract
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.
- Published
- 2010
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