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PMID:9607916
| Citation |
Phung, QH, Winter, DB, Cranston, A, Tarone, RE, Bohr, VA, Fishel, R and Gearhart, PJ (1998) Increased hypermutation at G and C nucleotides in immunoglobulin variable genes from mice deficient in the MSH2 mismatch repair protein. J. Exp. Med. 187:1745-51 |
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| 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 VkappaOx1 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. |
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| Keywords |
Animals; Base Composition; Base Sequence; Cytosine; DNA Repair; DNA-Binding Proteins; Gene Deletion; Gene Rearrangement, B-Lymphocyte; Guanine; Immunoglobulin Variable Region/genetics; Immunoglobulin kappa-Chains/genetics; Mice; Mice, Inbred C57BL; Molecular Sequence Data; MutS Homolog 2 Protein; Mutation; Nucleic Acid Heteroduplexes; Oxazolone/immunology; Proto-Oncogene Proteins/deficiency; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins/physiology |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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