ATM: Translating the DNA Damage Response to Adaptive Immunity

ATM is often dubbed the master regulator of the DNA double stranded break (DSB) response. Since proper induction and repair of DNA DSBs forms the core of immunological diversity, it is surprising that patients with ataxia telangiectasia generally have a mild immunodeficiency in contrast to other DSB repair syndromes. In this review, we address this discrepancy by delving into the functions of ATM in DSB repair and cell cycle control and translate these to adaptive immunity. We conclude that ATM, despite its myriad functions, is not an absolute requirement for acquiring sufficient levels of immunological diversity to prevent severe viral and opportunistic infections. There is, however, a more clinically pronounced antibody deficiency in ataxia telangiectasia due to disturbed class switch recombination.

Automated summary

ATM is often considered the key regulator of the DNA double-stranded break response, yet patients with ataxia telangiectasia surprisingly exhibit only mild immunodeficiency compared to other DSB repair syndromes. Despite its numerous functions, ATM is not essential for acquiring sufficient levels of immunological diversity to prevent severe infections, although there is a notable antibody deficiency in ataxia telangiectasia patients due to disrupted class switch recombination.