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Molecular mechanisms of antibody somatic hypermutation.
Functional antibody genes are assembled by V-D-J joining and then diversified by somatic hypermutation. This hypermutation results from stepwise incorporation of single nucleotide substitutions into
Immunoglobulin Isotype Switching Is Inhibited and Somatic Hypermutation Perturbed in UNG-Deficient Mice
The results provide strong support for the DNA deamination model for antibody diversification with respect to class-switching as well as hypermutation and suggest that UNG is the major mouse DNA glycosylase responsible for processing the programmed dU/dG lesions within the immunoglobulin locus.
DNA Deamination Mediates Innate Immunity to Retroviral Infection
Evidence is provided that CEM15/APOBEC3G is a DNA deaminase that is incorporated into virions during viral production and subsequently triggers massive deamination of deoxycytidine to deoxyuridine within the retroviral minus (first)-strand cDNA, thus providing a probable trigger for viral destruction.
Mutational Processes Molding the Genomes of 21 Breast Cancers
This work generated catalogs of somatic mutation from 21 breast cancers and applied mathematical methods to extract mutational signatures of the underlying processes, finding a remarkable phenomenon of localized hypermutation, termed “kataegis,” was observed.
Mismatch recognition and uracil excision provide complementary paths to both Ig switching and the A/T-focused phase of somatic mutation.
While antibody diversification is perturbed by single deficiency in either UNG or MSH2, combined UNG/MSH2 deficiency leads to a total ablation both of switch recombination and of IgV hypermutation at dA:dT pairs.
Evolution of the AID/APOBEC family of polynucleotide (deoxy)cytidine deaminases.
It is found that although the family forms part of a larger superfamily of deaminases distributed throughout the biological world, the AID/APOBEC family itself is restricted to vertebrates with homologs of AID (a DNA deaminase that triggers antibody gene diversification) and of APOBEC2 (unknown function) identifiable in sequence databases from bony fish, birds, amphibians, and mammals.
B cells acquire antigen from target cells after synapse formation
It is shown that B-cell interaction with antigens that are immobilized on the surface of a target cell leads to the formation of a synapse and the acquisition, even, of membrane-integral antigen from the target.
The Vif Protein of HIV Triggers Degradation of the Human Antiretroviral DNA Deaminase APOBEC3G
It is shown that Vif triggers APOBec3G degradation by a proteasome-dependent pathway and that an 80 amino acid region of APOBEC3G surrounding its first zinc coordination motif is sufficient to confer the ability to partake in an interaction involving Vif.
AID mutates E. coli suggesting a DNA deamination mechanism for antibody diversification
It is shown that expression of AID in Escherichia coli gives a mutator phenotype that yields nucleotide transitions at dC/dG in a context-dependent manner, which indicates that AID functions by deaminating dC residues in DNA.