dna-dependent protein kinase inhibits aid-induced antibody gene conversion依赖dna的蛋白激酶抑制aid-induced抗体基因转换.pdfVIP

PLoS BIOLOGY DNA-Dependent Protein Kinase Inhibits AID- Induced Antibody Gene Conversion 1 1¤ 1 1 2,3 4 Adam J. L. Cook , Joanna M. Raftery , K. K. Edwin Lau , Andrew Jessup , Reuben S. Harris , Shunichi Takeda , 1* Christopher J. Jolly 1 Centenary Institute and University of Sydney Faculty of Medicine, Sydney, New South Wales, Australia, 2 Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota, United States of America, 3 Institute for Molecular Virology, University of Minnesota, Minneapolis, Minnesota, United States of America, 4 Department of Radiation Genetics, Kyoto University School of Medicine, Kyoto, Japan Affinity maturation and class switching of antibodies requires activation-induced cytidine deaminase (AID)-dependent hypermutation of Ig V(D)J rearrangements and Ig S regions, respectively, in activated B cells. AID deaminates deoxycytidine bases in Ig genes, converting them into deoxyuridines. In V(D)J regions, subsequent excision of the deaminated bases by uracil-DNA glycosylase, or by mismatch repair, leads to further point mutation or gene conversion, depending on the species. In Ig S regions, nicking at the abasic sites produced by AID and uracil-DNA glycosylases results in staggered double-strand breaks, whose repair by nonhomologous end joining mediates Ig class switching. We have tested whether nonhomologous end joining also plays a role in V(D)J hypermutation using chicken DT40 cells deficient for Ku70 or the DNA-dependent protein k