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

40 Citations (Scopus)

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

Fingerprint

Endonucleases
Maintenance
Genome
DNA Mismatch Repair
Mutation Rate
Spermatogenesis
Genetic Recombination
Mammals
Neoplasms
B-Lymphocytes

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 journalArticle

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. / PMS2 endonuclease activity has distinct biological functions and is essential for genome maintenance. In: Proceedings of the National Academy of Sciences of the United States of America. 2010 ; Vol. 107, No. 30. pp. 13384-13389.
@article{4d1be1b2638346d187c2fdb34849d898,
title = "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.",
keywords = "B cell lymphoma, Class switch recombination, DNA mismatch repair, Somatic hypermutation, Spermatogenesis",
author = "{Van Oers}, {Johanna M M} and Sergio Roa and Uwe Werling and Yiyong Liu and Jochen Genschel and Harry Hou and Sellers, {Rani S.} and Paul Modrich and Scharff, {Matthew D.} and Winfried Edelmann",
year = "2010",
month = "7",
day = "27",
doi = "10.1073/pnas.1008589107",
language = "English (US)",
volume = "107",
pages = "13384--13389",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "30",

}

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 -