Our research group tries to understand the control of mutagenesis and class switch recombination of antibody genes.
To achieve highly effective antibodies, very extensive mutagenesis of the antibody genes in B lymphocytes is used. The human mutagenesis system is based on the targeted deamination of DNA by the enzyme activation-induced cytidine deaminase, AID, followed by the processing of AID's DNA damage by the B lymphocytes in an extremely error-prone manner.
Unfortunately, tumour-associated genes are also mutagenised and the mutagenesis does not only occur in B lymphocytes. Mis-expression of AID and elevated mutation rates are therefore linked to tumours in a number of other cell types as well.
Our studies have provided us with knowledge of how the mutagenesis is targeted through our identification of mutasomes, large protein complexes containing AID, transcription factors, and DNA repair enzymes. We are doing in-depth analysis of how the mutagenesis system is targeted to the antibody genes and controlled.