Abstract
Mice homozygous for a disrupted allele of the mismatch repair gene Pms2 have a mutator phenotype. When this allele is crossed into quasi-monoclonal (QM) mice, which have a very limited B cell repertoire, homozygotes have fewer somatic mutations at the immunoglobulin heavy chain and lambda chain loci than do heterozygotes or wild-type QM mice. That is, mismatch repair seems to contribute to somatic hypermutation rather than stifling it. It is suggested that at immunoglobulin loci in hypermutable B cells, mismatched base pairs are "corrected" according to the newly synthesized DNA strand, thereby fixing incipient mutations instead of eliminating them.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenosine Triphosphatases*
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Alleles
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Amino Acid Sequence
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Animals
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B-Lymphocytes / immunology
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Base Composition
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Base Sequence
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Cloning, Molecular
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Crosses, Genetic
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DNA Repair Enzymes*
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DNA Repair*
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DNA-Binding Proteins*
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Female
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Gene Rearrangement
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Genes, Immunoglobulin*
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Heterozygote
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Immunoglobulin Heavy Chains / chemistry
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Immunoglobulin Heavy Chains / genetics
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Immunoglobulin Variable Region / chemistry
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Immunoglobulin Variable Region / genetics*
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Immunoglobulin lambda-Chains / chemistry
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Immunoglobulin lambda-Chains / genetics
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Male
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Mice
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Mice, Knockout
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Mismatch Repair Endonuclease PMS2
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Molecular Sequence Data
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Mutation*
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Proteins / genetics*
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Proteins / physiology
Substances
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DNA-Binding Proteins
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Immunoglobulin Heavy Chains
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Immunoglobulin Variable Region
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Immunoglobulin lambda-Chains
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Proteins
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Adenosine Triphosphatases
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Pms2 protein, mouse
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Mismatch Repair Endonuclease PMS2
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DNA Repair Enzymes