The regulation of somatic hypermutation.
Somatic hypermutation and class switch recombination cause genetic alterations in immunoglobulin (Ig) genes, which underlie the generation of the secondary antibody repertoire in B lymphocytes. Both processes require activation-induced cytidine deaminase (AID), whose mechanism of action in not yet known in detail, but which mediates the accumulation of point mutations in the Ig locus. This highly mutagenic process must be tightly controlled, and multiple levels of regulation might exist. Recent experiments show that AID deaminates deoxycytidine to deoxyuridine in single-stranded DNA. This mutagenic event is targeted to actively transcribed sequences, and the specificity of deamination might be related to the chromatin structure of the transcription complex.
Besmer
Eva
E
Laboratory of Lymphocyte Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
Gourzi
Polyxeni
P
Papavasiliou
F Nina
FN
D003564:Cytidine Deaminase / Q000378:metabolism; D004277:DNA, Single-Stranded / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D009154:Mutation; D015398:Signal Transduction; D027041:Somatic Hypermutation, Immunoglobulin; D014158:Transcription, Genetic; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D004277:DNA, Single-Stranded; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase