UMMS Affiliation

Department of Molecular Genetics and Microbiology

Publication Date

2003-05-19

Document Type

Article

Subjects

Adenosine Triphosphatases; Animals; Base Pair Mismatch; Base Sequence; Carrier Proteins; DNA Repair; *DNA Repair Enzymes; DNA-Binding Proteins; Immunoglobulin Class Switching; Mice; Molecular Sequence Data; MutS Homolog 2 Protein; Neoplasm Proteins; Nuclear Proteins; Proto-Oncogene Proteins; *Recombination, Genetic

Disciplines

Amino Acids, Peptides, and Proteins | Genetic Phenomena | Life Sciences | Medicine and Health Sciences | Women's Studies

Abstract

Mismatch repair proteins participate in antibody class switch recombination, although their roles are unknown. Previous nucleotide sequence analyses of switch recombination junctions indicated that the roles of Msh2 and the MutL homologues, Mlh1 and Pms2, differ. We now asked if Msh2 and Mlh1 function in the same pathway during switch recombination. Splenic B cells from mice deficient in both these proteins were induced to undergo switching in culture. The frequency of switching is reduced, similarly to that of B cells singly deficient in Msh2 or Mlh1. However, the nucleotide sequences of the Smu-Sgamma3 junctions resemble junctions from Mlh1- but not from Msh2-deficient cells, suggesting Mlh1 functions either independently of or before Msh2. The substitution mutations within S regions that are known to accompany switch recombination are increased in Msh2- and Mlh1 single-deficient cells and further increased in the double-deficient cells, again suggesting these proteins function independently in class switch recombination. The finding that MMR functions to reduce mutations in switch regions is unexpected since MMR proteins have been shown to contribute to somatic hypermutation of antibody variable region genes.

Keywords

B cells, immunoglobulin isotypes, mismatch repair, switch region mutations, switch junctions

Rights and Permissions

Publisher PDF posted as allowed by the publisher's terms of use policy at: http://www.rupress.org/terms After the Initial Publication Period, RUP will grant to the public the non-exclusive right to copy, distribute, or display the Article under a Creative Commons Attribution-Noncommercial-Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode, or updates thereof.

DOI of Published Version

10.1084/jem.20022190

Source

J Exp Med. 2003 May 19;197(10):1377-83. Epub 2003 May 12. Link to article on publisher's site

Journal/Book/Conference Title

The Journal of experimental medicine

Related Resources

Link to article in PubMed

PubMed ID

12743174

Creative Commons License

Creative Commons Attribution-Noncommercial 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 4.0 License.

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