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

Back

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

Journal article

Open access

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 and Winfried Edelmann

Proceedings of the National Academy of Sciences - PNAS, Vol.107(30), pp.13384-13389

07/27/2010

DOI: https://doi.org/10.1073/pnas.1008589107

Handle:

https://hdl.handle.net/2376/115090

PMCID: PMC2922181

PMID: 20624957

Files and links (1)

url

https://doi.org/10.1073/pnas.1008589107View

Published (Version of record) Open

Abstract

spermatogenesis

Biological Sciences

somatic hypermutation

class switch recombination

B cell lymphoma

DNA mismatch repair

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.

Metrics

8 Record Views

See more details

Details

Title: PMS2 endonuclease activity has distinct biological functions and is essential for genome maintenance
Creators: Johanna M. M van Oers - Departments of
Sergio Roa - Departments of
Uwe Werling - Departments of
Yiyong Liu - Department of Biochemistry and
Jochen Genschel - Department of Biochemistry and
Harry Hou - Cancer Center
Rani S Sellers - Pathology, and
Paul Modrich - Department of Biochemistry and
Matthew D Scharff - Departments of
Winfried Edelmann - Departments of
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.107(30), pp.13384-13389
Academic Unit: Biomedical Sciences, Department of
Publisher: National Academy of Sciences
Identifiers: 99900547660501842
Language: English
Resource Type: Journal article