Role for mismatch repair proteins Msh2, Mlh1, and Pms2 in immunoglobulin class switching shown by sequence analysis of recombination junctions
UMass Chan Affiliations
Department of Molecular Genetics and MicrobiologyDocument Type
Journal ArticlePublication Date
2002-02-04Keywords
Adenosine TriphosphatasesAnimals
B-Lymphocytes
*Base Pair Mismatch
Base Sequence
Carrier Proteins
DNA
DNA Repair
*DNA Repair Enzymes
DNA-Binding Proteins
*Immunoglobulin Class Switching
Mice
Mice, Inbred C57BL
Mice, Knockout
Molecular Sequence Data
MutS Homolog 2 Protein
Neoplasm Proteins
Nuclear Proteins
Proto-Oncogene Proteins
Recombination, Genetic
Sequence Homology, Nucleic Acid
splenic B cells
DNA recombination
DNA repair
antibody heavy chain isotypes
mismatch repair
Life Sciences
Medicine and Health Sciences
Women's Studies
Metadata
Show full item recordAbstract
B cells from mice deficient in mismatch repair (MMR) proteins show decreased ability to undergo class switch recombination in vitro and in vivo. The deficit is not accompanied by any reduction in cell viability or alterations in the cell cycle in B cells cultured in vitro. To assess the role of MMR in switching we examined the nucleotide sequences of Smicro-Sgamma3 recombination junctions in splenic B cells induced in culture to switch to IgG3. The data demonstrate clear differences in the sequences of switch junctions in wild-type B cells in comparison with Msh2-, Mlh1-, and Pms2-deficient B cells. Sequences of switch junctions from Msh2-deficient cells showed decreased lengths of microhomology between Smicro and Sgamma3 relative to junctions from wild-type cells and an increase in insertions, i.e., nucleotides which do not appear to be derived from either the Smicro or Sgamma3 parental sequence. By contrast, 23% of junctions from Mlh1- and Pms2-deficient cells occurred at unusually long stretches of microhomology. The data indicate that MMR proteins are directly involved in class switching and that the role of Msh2 differs from that of Mlh1 and Pms2.Source
J Exp Med. 2002 Feb 4;195(3):367-73.
DOI
10.1084/jem.20011877Permanent Link to this Item
http://hdl.handle.net/20.500.14038/50659PubMed ID
11828012Related Resources
Rights
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.Distribution License
http://creativecommons.org/licenses/by-nc-sa/4.0/ae974a485f413a2113503eed53cd6c53
10.1084/jem.20011877
Scopus Count
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Except where otherwise noted, this item's license is described as 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.
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