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Open Access Green as soon as Postprint is submitted to ZB.
Activation-induced cytidine deaminase-mediated hypermutation in the DT40 cell line.
Philos. Trans. R. Soc. B - Biol. Sci. 364(517), 639-644 (2008)
Depending on the species and the developmental stage of B cells, activation-induced cytidine deaminase (AID) triggers immunoglobulin (Ig) gene diversification by gene conversion, hypermutation or switch recombination. The bursal B cell line DT40 usually diversifies its rearranged Ig light chain (IgL) gene by gene conversion, but disruption of the RAD51 gene paralogues or deletion of the psiV conversion donors induces hypermutation. Although not all aspects of somatic hypermutation can be studied in DT40, the compact size of the chicken IgL locus and the ability to modify the genome by targeted integration are powerful experimental advantages. We review here how the studies in DT40 contributed to understanding how AID initiates Ig gene diversification and how AID-induced uracils are subsequently processed by uracil DNA glycosylase, proliferating cell nuclear antigens and error-prone polymerases. We also discuss the on-going research on the Ig locus specificity of hypermutation and the possibility of using hypermutation for the artificial evolution of proteins and regulatory sequences in DT40.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
activation-induced cytidine deaminase; DT40; gene conversion; immunoglobulin; somatic hypermutation
ISSN (print) / ISBN
0962-8436
e-ISSN
1471-2970
Quellenangaben
Volume: 364(517),
Issue: 1517,
Pages: 639-644
Publisher
Royal Society of London
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Molecular Radiation Biology (IMS)