PMID:15494304

Citation	Rada, C, Di Noia, JM and Neuberger, MS (2004) Mismatch recognition and uracil excision provide complementary paths to both Ig switching and the A/T-focused phase of somatic mutation. Mol. Cell 16:163-71
Abstract	AID-mediated deamination of dC residues within the immunoglobulin locus generates dU:dG lesions whose resolution leads to class-switch recombination and somatic hypermutation. The dU:dG pair is a mismatch and comprises a base foreign to DNA and is, thus, recognized by proteins from both base excision (uracil-DNA glycosylase, UNG) and mismatch recognition (MSH2/MSH6) pathways. Strikingly, 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. The initiating dU:dG lesions appear not to be recognized and are simply replicated over. The results indicate that the major pathway for switch recombination occurs through uracil excision with mismatch recognition of dU:dG providing a backup; the second phase of hypermutation (essentially introducing mutations solely at dA:dT pairs) is triggered by mismatch recognition of the dU:dG lesion with uracil excision providing a backup.
Links	PubMed Online version:10.1016/j.molcel.2004.10.011
Keywords	Animals; B-Lymphocytes/metabolism; DNA Glycosylases/genetics; DNA Glycosylases/metabolism; DNA Repair/physiology; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Immunoglobulin Class Switching/genetics; Immunoglobulin Variable Region/genetics; Immunoglobulins/genetics; Mice; MutS Homolog 2 Protein; Mutation; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins/metabolism; Uracil/metabolism; Uracil-DNA Glycosidase
edit table

Annotations

Gene product	Qualifier	GO ID	GO term name	Evidence Code	with/from	Aspect	Notes	Status
edit table

References

See Help:References for how to manage references in GONUTS.