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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.

SUBMITTER: van Oers JM

PROVIDER: S-EPMC2922181 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

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

van Oers Johanna M M JM 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

Proceedings of the National Academy of Sciences of the United States of America 20100712 30

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, P ...[more]

PMID: 20624957

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