Balancing AID and DNA repair during somatic hypermutation.
Somatic hypermutation (SHM) of Ig genes in B cells is crucial for antibody affinity maturation. The reaction is initiated by cytosine deamination of Ig loci by activation induced deaminase (AID) and is completed by error-prone DNA repair enzyme processing of AID-generated uracils. The mechanisms that target SHM specifically to Ig loci are poorly understood. Recently, it has been demonstrated that although AID preferentially targets Ig loci, it acts surprisingly widely on non-Ig loci, many of which are protected from mutation accumulation by high-fidelity DNA repair. We propose that breakdown of this high fidelity repair process helps explain oncogene mutations observed in B-cell tumors, and further, that many oncogenes are vulnerable to AID-mediated DNA breaks and translocations in normal activated B cells.
Liu
Man
M
Department of Immunobiology and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA.
Schatz
David G
DG
D000818:Animals; D000915:Antibody Affinity / Q000235:genetics*; D000916:Antibody Diversity / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic; D003564:Cytidine Deaminase / Q000276:immunology / Q000378:metabolism*; D004247:DNA; D004260:DNA Repair / Q000276:immunology*; D044127:Epigenesis, Genetic; D005803:Genes, Immunoglobulin; D006801:Humans; D009154:Mutation; D009857:Oncogenes / Q000235:genetics / Q000276:immunology; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics; D013379:Substrate Specificity; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D004247:DNA; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase