title: The biochemistry of somatic hypermutation.
abstract: Affinity maturation of the humoral response is mediated by somatic hypermutation of the immunoglobulin (Ig) genes and selection of higher-affinity B cell clones. Activation-induced cytidine deaminase (AID) is the first of a complex series of proteins that introduce these point mutations into variable regions of the Ig genes. AID deaminates deoxycytidine residues in single-stranded DNA to deoxyuridines, which are then processed by DNA replication, base excision repair (BER), or mismatch repair (MMR). In germinal center B cells, MMR, BER, and other factors are diverted from their normal roles in preserving genomic integrity to increase diversity within the Ig locus. Both AID and these components of an emerging error-prone mutasome are regulated on many levels by complex mechanisms that are only beginning to be elucidated.
authors.affiliation: Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA. jpeled@aecom.yu.edu
authors.forename: Jonathan U
authors.initials: JU
authors.lastname: Peled
authors.forename: Fei Li
authors.initials: FL
authors.lastname: Kuang
authors.forename: Maria D
authors.initials: MD
authors.lastname: Iglesias-Ussel
authors.forename: Sergio
authors.initials: S
authors.lastname: Roa
authors.forename: Susan L
authors.initials: SL
authors.lastname: Kalis
authors.forename: Myron F
authors.initials: MF
authors.lastname: Goodman
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Scharff
mesh_terms: D000818:Animals; D003564:Cytidine Deaminase / Q000378:metabolism; D053843:DNA Mismatch Repair; D004260:DNA Repair; D018858:Germinal Center / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D008957:Models, Genetic; D027041:Somatic Hypermutation, Immunoglobulin; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D007135:Immunoglobulin Variable Region; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase