Research
Limited by the genetic pool, immune cells resort to the dangerous game of mutagenizing their own genome to create diversity in their antigen receptors. In mice and humans, B cells deploy AID, a cytosine DNA deaminase, to initiate somatic hypermutation and class switch recombination by subverting DNA repair into mutagenic processing of uracil. Innate immunity uses a similar strategy to restrict the infectivity of retroviruses. The trade-off for the accelerated evolution of the antigen receptors is the increase in the risk of cancer.
Our lab together with Prof. Michael Neuberger, studies how B cells turn the repair of the uracils into mutagenesis and how AID activity is directed preferentially to the antigen receptor genes. We are looking at the role of uracil in several other cellular processes and in particular immune responses to viruses. The lab also investigates the biology of other members of the AID/APOBEC family of cytidine deaminases.
Publications
Häsler J, Rada C, Neuberger MS. The cytoplasmic AID complex. Semin Immunol. 2012 Aug;24(4):273-80.
Kemmerich K, Dingler FA, Rada C, Neuberger MS. Germline ablation of SMUG1 DNA glycosylase causes loss of 5-hydroxymethyluracil- and UNG-backup uracil-excision activities and increases cancer predisposition of Ung-/-Msh2-/- mice. Nucleic Acids Res. 2012 Jul;40(13):6016-25.
Häsler J, Rada C, Neuberger MS. Cytoplasmic activation-induced cytidine deaminase (AID) exists in stoichiometric complex with translation elongation factor 1α (eEF1A). Proc Natl Acad Sci U S A. 2011 Nov 8;108(45):18366-71.
Ellyard JI, Benk AS, Taylor B, Rada C, Neuberger MS. The dependence of Ig class-switching on the nuclear export sequence of AID likely reflects interaction with factors additional to Crm1 exportin. Eur J Immunol. 2011 Feb;41(2):485-90.
Wang M, Rada C, Neuberger MS. Altering the spectrum of immunoglobulin V gene somatic hypermutation by modifying the active site of AID. J Exp Med. 2010 Jan 18;207(1):141-53.
