Immunoglobulin diversification in DT40: a model for vertebrate DNA damage tolerance.
Studies of recombination in vertebrates have rather lagged behind those in yeast and bacteria in large part due to the relative genetic intractability of vertebrate model systems. Immunoglobulin diversification in the chicken cell line DT40 provides a powerful combination of a physiological recombination process coupled with facile genetic modification. The immunoglobulin variable regions of DT40 constitutively diversify by a combination of gene conversion, in which sequence changes are templated from one of a number of upstream pseudogenes or by non-templated point mutation. Both of these events are initiated by abasic sites in the variable region DNA generated following the targeted deamination of cytidine by activation induced deaminase. Recent work has shown that the two outcomes, gene conversion and somatic mutation, are likely to reflect alternate pathways for the processing of these abasic sites. In this review I will discuss the current data on avian Ig gene diversification and examine how the immunoglobulin loci of DT40 may provide a useful model system for studying the mechanisms and interactions of vertebrate recombination and pathways of DNA damage tolerance.
Sale
Julian E
JE
Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK. jes@mrc-lmb.cam.ac.uk
D000818:Animals; D045744:Cell Line, Tumor; D002645:Chickens; D003564:Cytidine Deaminase / Q000378:metabolism; D004249:DNA Damage; D005785:Gene Conversion; D005803:Genes, Immunoglobulin; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007136:Immunoglobulins / Q000235:genetics*; D016393:Lymphoma, B-Cell; D008957:Models, Genetic; D017354:Point Mutation; D011544:Pseudogenes; D011995:Recombination, Genetic; D014714:Vertebrates / Q000235:genetics / Q000276:immunology*
D007135:Immunoglobulin Variable Region; D007136:Immunoglobulins; D003564:Cytidine Deaminase