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

Proc Natl Acad Sci U S A 2010 Jul 12;107(30):13384-9. Epub 2010 Jul 12.

Department of Cell Biology, and Cancer Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

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.

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http://dx.doi.org/10.1073/pnas.1008589107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2922181PMC
July 2010
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