Mismatch repair co-opted by hypermutation. 1998

M Cascalho, and J Wong, and C Steinberg, and M Wabl
Department of Microbiology and Immunology, University of California, San Francisco, CA 94143-0670, USA.

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.

UI MeSH Term Description Entries
D007135 Immunoglobulin Variable Region That region of the immunoglobulin molecule that varies in its amino acid sequence and composition, and comprises the binding site for a specific antigen. It is located at the N-terminus of the Fab fragment of the immunoglobulin. It includes hypervariable regions (COMPLEMENTARITY DETERMINING REGIONS) and framework regions. Variable Region, Ig,Variable Region, Immunoglobulin,Framework Region, Immunoglobulin,Fv Antibody Fragments,Fv Fragments,Ig Framework Region,Ig Variable Region,Immunoglobulin Framework Region,Immunoglobulin Fv Fragments,Immunoglobulin V,Antibody Fragment, Fv,Antibody Fragments, Fv,Fragment, Fv,Fragment, Fv Antibody,Fragment, Immunoglobulin Fv,Fragments, Fv,Fragments, Fv Antibody,Fragments, Immunoglobulin Fv,Framework Region, Ig,Framework Regions, Ig,Framework Regions, Immunoglobulin,Fv Antibody Fragment,Fv Fragment,Fv Fragment, Immunoglobulin,Fv Fragments, Immunoglobulin,Ig Framework Regions,Ig Variable Regions,Immunoglobulin Framework Regions,Immunoglobulin Fv Fragment,Immunoglobulin Variable Regions,Regions, Immunoglobulin Variable,Variable Regions, Ig,Variable Regions, Immunoglobulin
D007143 Immunoglobulin Heavy Chains The largest of polypeptide chains comprising immunoglobulins. They contain 450 to 600 amino acid residues per chain, and have molecular weights of 51-72 kDa. Immunoglobulins, Heavy-Chain,Heavy-Chain Immunoglobulins,Ig Heavy Chains,Immunoglobulin Heavy Chain,Immunoglobulin Heavy Chain Subgroup VH-I,Immunoglobulin Heavy Chain Subgroup VH-III,Heavy Chain Immunoglobulins,Heavy Chain, Immunoglobulin,Heavy Chains, Ig,Heavy Chains, Immunoglobulin,Immunoglobulin Heavy Chain Subgroup VH I,Immunoglobulin Heavy Chain Subgroup VH III,Immunoglobulins, Heavy Chain
D007146 Immunoglobulin lambda-Chains One of the types of light chain subunits of the immunoglobulins with a molecular weight of approximately 22 kDa. Ig lambda Chains,Immunoglobulins, lambda-Chain,Immunoglobulin lambda-Chain,lambda-1-Immunoglobulin,lambda-2-Immunoglobulin,lambda-Chain Immunoglobulins,lambda-Immunoglobulin Light Chain,lambda-Immunoglobulin Light Chains,lambda-x Immunoglobulin,Chains, Ig lambda,Chains, lambda-Immunoglobulin Light,Immunoglobulin lambda Chain,Immunoglobulin lambda Chains,Immunoglobulin, lambda-x,Immunoglobulins, lambda Chain,Light Chain, lambda-Immunoglobulin,Light Chains, lambda-Immunoglobulin,lambda 1 Immunoglobulin,lambda 2 Immunoglobulin,lambda Chain Immunoglobulins,lambda Chains, Ig,lambda Immunoglobulin Light Chain,lambda Immunoglobulin Light Chains,lambda x Immunoglobulin,lambda-Chain, Immunoglobulin,lambda-Chains, Immunoglobulin
D008297 Male Males
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D011506 Proteins Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein. Gene Products, Protein,Gene Proteins,Protein,Protein Gene Products,Proteins, Gene
D003001 Cloning, Molecular The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells. Molecular Cloning
D003433 Crosses, Genetic Deliberate breeding of two different individuals that results in offspring that carry part of the genetic material of each parent. The parent organisms must be genetically compatible and may be from different varieties or closely related species. Cross, Genetic,Genetic Cross,Genetic Crosses
D004260 DNA Repair The removal of DNA LESIONS and/or restoration of intact DNA strands without BASE PAIR MISMATCHES, intrastrand or interstrand crosslinks, or discontinuities in the DNA sugar-phosphate backbones. DNA Damage Response

Related Publications

M Cascalho, and J Wong, and C Steinberg, and M Wabl
August 1998, Cell,
M Cascalho, and J Wong, and C Steinberg, and M Wabl
June 1998, Proceedings of the National Academy of Sciences of the United States of America,
M Cascalho, and J Wong, and C Steinberg, and M Wabl
July 2005, European journal of immunology,
M Cascalho, and J Wong, and C Steinberg, and M Wabl
November 1999, Immunology today,
M Cascalho, and J Wong, and C Steinberg, and M Wabl
September 2020, Nature genetics,
M Cascalho, and J Wong, and C Steinberg, and M Wabl
December 2021, Clinical cancer research : an official journal of the American Association for Cancer Research,
M Cascalho, and J Wong, and C Steinberg, and M Wabl
November 2008, The Journal of biological chemistry,
M Cascalho, and J Wong, and C Steinberg, and M Wabl
March 2020, Clinical cancer research : an official journal of the American Association for Cancer Research,
M Cascalho, and J Wong, and C Steinberg, and M Wabl
October 2023, Science (New York, N.Y.),
M Cascalho, and J Wong, and C Steinberg, and M Wabl
March 1999, Journal of immunology (Baltimore, Md. : 1950),
Copied contents to your clipboard!