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.
van Oers
Johanna M M
JM
Department of Cell Biology, and Cancer Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Roa
Sergio
S
Werling
Uwe
U
Liu
Yiyong
Y
Genschel
Jochen
J
Hou
Harry
H
Sellers
Rani S
RS
Modrich
Paul
P
Scharff
Matthew D
MD
Edelmann
Winfried
W
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
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