title: PMS2 endonuclease activity has distinct biological functions and is essential for genome maintenance.
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.
authors.affiliation: Department of Cell Biology, and Cancer Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Johanna M M
authors.initials: JM
authors.lastname: van Oers
authors.forename: Sergio
authors.initials: S
authors.lastname: Roa
authors.forename: Uwe
authors.initials: U
authors.lastname: Werling
authors.forename: Yiyong
authors.initials: Y
authors.lastname: Liu
authors.forename: Jochen
authors.initials: J
authors.lastname: Genschel
authors.forename: Harry
authors.initials: H
authors.lastname: Hou
authors.forename: Rani S
authors.initials: RS
authors.lastname: Sellers
authors.forename: Paul
authors.initials: P
authors.lastname: Modrich
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Scharff
authors.forename: Winfried
authors.initials: W
authors.lastname: Edelmann
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D053843:DNA Mismatch Repair / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000166:cytology; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005298:Fertility / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D020022:Genetic Predisposition to Disease / Q000235:genetics; D042822:Genomic Instability; D005838:Genotype; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000235:genetics; D007074:Immunoglobulin G / Q000235:genetics; D008223:Lymphoma / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D000070976:Mismatch Repair Endonuclease PMS2; D009154:Mutation; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D004268:DNA-Binding Proteins; D007074:Immunoglobulin G; D004720:Endonucleases; D000251:Adenosine Triphosphatases; C499533:Pms2 protein, mouse; D000070976:Mismatch Repair Endonuclease PMS2; D045643:DNA Repair Enzymes