Increased hypermutation at G and C nucleotides in immunoglobulin variable genes from mice deficient in the MSH2 mismatch repair protein

Quy H. Phung, David B. Winter, Aaron Cranston, Robert E. Tarone, Vilhelm A. Bohr, Richard Fishel, Patricia J. Gearhart

Research output: Contribution to journalArticle

Abstract

Rearranged immunoglobulin variable genes are extensively mutated after stimulation of B lymphocytes by antigen. Mutations are likely generated by an error-prone DNA polymerase, and the mismatch repair pathway may process the mispairs. To examine the role of the MSH2 mismatch repair protein in hypermutation, Msh2(-/-) mice were immunized with oxazolone, and B cells were analyzed for mutation in their V(κ)Ox1 light chain genes. The frequency of mutation in the repair-deficient mice was similar to that in Msh2(+/+) mice, showing that MSH2-dependent mismatch repair does not cause hypermutation. However, there was a striking bias for mutations to occur at germline G and C nucleotides. The results suggest that the hypermutation pathway frequently mutates G-C pairs, and a MSH2-dependent pathway preferentially corrects mismatches at G and C.

Original languageEnglish (US)
Pages (from-to)1745-1750
Number of pages6
JournalJournal of Experimental Medicine
Volume187
Issue number11
DOIs
StatePublished - Jun 1 1998

Keywords

  • Biological sciences
  • DNA repair
  • Genes, immunoglobulin
  • Genetics
  • Mutation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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