Albert Einstein Cancer Center

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, AECC members Edelmann and Scharff generated endonuclease-deficient Pms2(E702K) knock-in mice that displayed increased genomic mutation rates and a strong cancer predisposition. In addition, class switch recombination, but not somatic hypermutation, was impaired in Pms2(EK/EK) B cells, indicating a specific role in Ig diversity. In contrast to Pms2 (-/-) mice, Pms2(EK/EK) male mice were fertile, indicating that this activity is dispensable in spermatogenesis. Hence, these studies demonstrated that PMS2 endonuclease activity has distinct biological functions and is essential for genome maintenance and tumor suppression. 

 
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