Activation induced deaminase C-terminal domain links DNA breaks to end protection and repair during class switch recombination

The enzyme activation-induced deaminase (AID) triggers antibody class switch recombination (CSR), a critical mechanism for immune response. CSR is an intrachromosomal rearrangement requiring DNA double strand breaks that are initiated by AID and must be repaired by specific DNA repair pathways. We identify a domain of AID that is required to link the DNA damage step with the subsequent repair during CSR as well as for chromosomal translocations, a collateral effect of CSR. AID influences the recruitment of appropriate end-joining pathways for CSR, preventing aberrant DNA processing that leads to cell death or nonproductive repair and dominant-negative effects. Our results can also explain the basis of an autosomal dominant immunodeficiency caused by C-terminally truncated AID variants.