tailieunhanh - Transcription-coupled mutagenesis by the DNA deaminase AID Erik D Larson and Nancy Maizels

Activation-induced deaminase (AID) initiates switch recombination and somatic hypermutation of immunoglobulin genes in activated B cells. Compelling evidence now shows that AID travels with RNA polymerase II to deaminate actively transcribed DNA. reports deposited research A common mechanism for class-switch recombination and somatic hypermutation In all cells, high-fidelity pathways repair DNA to maintain the integrity of the genome. A handful | Minireview Transcription-coupled mutagenesis by the DNA deaminase AID Erik D Larson and Nancy Maizels Address Departments of Immunology and Biochemistry University of Washington Medical School 1959 NE Pacific Street Seattle WA 98195-7650 USA. Correspondence Nancy Maizels. E-mail maizels@ Published 27 February 2004 Genome Biology 2004 5 211 The electronic version of this article is the complete one and can be found online at http 2004 5 3 211 2004 BioMed Central Ltd Abstract Activation-induced deaminase AID initiates switch recombination and somatic hypermutation of immunoglobulin genes in activated B cells. Compelling evidence now shows that AID travels with RNA polymerase II to deaminate actively transcribed DNA. A common mechanism for class-switch recombination and somatic hypermutation In all cells high-fidelity pathways repair DNA to maintain the integrity of the genome. A handful of genes exempt themselves from this standard of immutability however most notably the loci that encode antigen receptors in B cells and T cells. Early in B- and T-cell development site-specific cleavage and rejoining of V D and J gene segments occurs to encode functional antigen receptors. Later upon B-cell activation the immunoglobulin loci undergo two additional and distinct genetic alterations Figure 1 . In class-switch recombination regulated DNA deletion replaces one heavy chain constant region with another changing the antibody s class but not its antigen specificity and thus optimizing clearance of antigen from the body. In somatic hypermutation targeted and rampant mutagenesis alters the sequences of the expressed heavy and light chain variable VDJ regions. Coupled with selection for B cells expressing high-affinity antigen receptors hypermutation enhances the efficiency and specificity of the immune response. The first evidence that switch recombination and somatic hypermutation share any mechanistic components came in 2000 when a pair of .