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

doi:10.1073/pnas.1008589107

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 journal › Article › peer-review

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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 Pms2^E702K knock-in mice. Pms2^EK/EK mice displayed increased genomic mutation rates and a strong cancer predisposition. In addition, class switch recombination, but not somatic hypermutation,was impaired in Pms2^EK/EK B cells, indicating a specific role in Ig diversity. In contrast to Pms2^-/- mice, Pms2^EK/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	https://doi.org/10.1073/pnas.1008589107
State	Published - Jul 27 2010

Keywords

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

ASJC Scopus subject areas

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Van Oers, J. M. M., Roa, S., Werling, U., Liu, Y., Genschel, J., Hou, H., Sellers, R. S., Modrich, P., Scharff, M. D., & Edelmann, W. (2010). PMS2 endonuclease activity has distinct biological functions and is essential for genome maintenance. Proceedings of the National Academy of Sciences of the United States of America, 107(30), 13384-13389. https://doi.org/10.1073/pnas.1008589107

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 › peer-review

Van Oers, JMM, Roa, S, Werling, U, Liu, Y, Genschel, J, Hou, H, Sellers, RS, Modrich, P, Scharff, MD & Edelmann, W 2010, 'PMS2 endonuclease activity has distinct biological functions and is essential for genome maintenance', Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 30, pp. 13384-13389. https://doi.org/10.1073/pnas.1008589107

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.

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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",

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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

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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.

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KW - Somatic hypermutation

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

Abstract

Keywords

ASJC Scopus subject areas

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