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

Johanna M.M. Van Oers, Sergio Roa, Uwe Werling, Yiyong Liu, Jochen Genschel, Harry Hou, Rani S. Sellers, Paul Modrich, Matthew D. Scharff, Winfried Edelmann

Research output: Contribution to journalArticle

42 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)13384-13389
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number30
DOIs
StatePublished - Jul 27 2010

Keywords

  • B cell lymphoma
  • Class switch recombination
  • DNA mismatch repair
  • Somatic hypermutation
  • Spermatogenesis

ASJC Scopus subject areas

  • General

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