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 language | English (US) |
|---|---|
| Pages (from-to) | 13384-13389 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 107 |
| Issue number | 30 |
| DOIs | |
| State | Published - Jul 27 2010 |
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Keywords
- B cell lymphoma
- Class switch recombination
- DNA mismatch repair
- Somatic hypermutation
- Spermatogenesis
ASJC Scopus subject areas
- General
- Medicine(all)
Cite this
PMS2 endonuclease activity has distinct biological functions and is essential for genome maintenance. / Van Oers, Johanna M M; Roa, Sergio; Werling, Uwe; Liu, Yiyong; Genschel, Jochen; Hou, Harry; Sellers, Rani S.; Modrich, Paul; Scharff, Matthew D.; Edelmann, Winfried.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 30, 27.07.2010, p. 13384-13389.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - PMS2 endonuclease activity has distinct biological functions and is essential for genome maintenance
AU - Van Oers, Johanna M M
AU - Roa, Sergio
AU - Werling, Uwe
AU - Liu, Yiyong
AU - Genschel, Jochen
AU - Hou, Harry
AU - Sellers, Rani S.
AU - Modrich, Paul
AU - Scharff, Matthew D.
AU - Edelmann, Winfried
PY - 2010/7/27
Y1 - 2010/7/27
N2 - 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.
AB - 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.
KW - B cell lymphoma
KW - Class switch recombination
KW - DNA mismatch repair
KW - Somatic hypermutation
KW - Spermatogenesis
UR - http://www.scopus.com/inward/record.url?scp=77955795716&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77955795716&partnerID=8YFLogxK
U2 - 10.1073/pnas.1008589107
DO - 10.1073/pnas.1008589107
M3 - Article
VL - 107
SP - 13384
EP - 13389
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 30
ER -