Molecular Mechanisms of Antibody Somatic Hypermutation
作者： Javier M. Di Noia , Michael S. Neuberger
DOI: 10.1146/ANNUREV.BIOCHEM.76.061705.090740
关键词:
摘要: AbstractFunctional antibody genes are assembled by V-D-J joining and then diversified somatic hypermutation. This hypermutation results from stepwise incorporation of single nucleotide substitutions into the V gene, underpinning much diversity affinity maturation. Hypermutation is triggered activation-induced deaminase (AID), an enzyme which catalyzes targeted deamination deoxycytidine residues in DNA. The pathways used for processing AID-generated U:G lesions determine variety base observed during Thus, DNA replication across uracil yields transition mutations at C:G pairs, whereas excision UNG uracil-DNA glycosylase creates abasic sites that can also yield transversions. Recognition mismatch MSH2/MSH6 triggers a mutagenic patch repair polymerase eta plays major role leads to A:T pairs. AID-triggered underpins immunoglobulin variable (IgV) gene conversion, ...
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