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National Academy of Sciences, Proceedings of the National Academy of Sciences, 30(107), p. 13384-13389, 2010

DOI: 10.1073/pnas.1008589107

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PMS2 endonuclease activity has distinct biological functions and is essential for genome maintenance

Journal article published in 2010 by Johanna M. M. van Oers, Sergio Roa ORCID, Uwe Werling, Yiyong Liu, Jochen Genschel, Harry Hou, Rani S. Sellers, Paul Modrich, Matthew D. Scharff, Winfried Edelmann
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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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 Pms2 E702K knock-in mice. Pms2 EK/EK mice 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. Therefore, the PMS2 endonuclease activity has distinct biological functions and is essential for genome maintenance and tumor suppression.