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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • van Oers, JMM; Roa, S; Werling, U; Liu, Y; Genschel, J; Hou, H; Sellers, RS; Modrich, P; Scharff, MD; Edelmann, W

Published Date

  • July 27, 2010

Published In

Volume / Issue

  • 107 / 30

Start / End Page

  • 13384 - 13389

PubMed ID

  • 20624957

Pubmed Central ID

  • 20624957

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

Digital Object Identifier (DOI)

  • 10.1073/pnas.1008589107

Language

  • eng

Conference Location

  • United States