ATM (ataxia telangiectasia mutated): expanding roles in the DNA damage response and cellular homeostasis

DNA damage is one of the most acute threats to cellular homeostasis and lif e. The cell responds to such damage by activating a vast array of responses , ranging from DNA repair to numerous signalling pathways, which temporaril y slow down the cellular life cycle while the damage is being repaired. Sop histicated relays convey the DNA damage alarm to all these systems immediat ely, after damage infliction. Such relays must be capable of sensing the da mage and rapidly creating functional contact with many signalling networks, The ataxia telangiectasia mutated (ATM) protein is a prominent example of such a relay. It responds swiftly to a critical DNA damage - the double str and break (DSB) - by phosphorylating key proteins in numerous signalling pa thways. Evidence is emerging, however, that the ATM protein might also be i nvolved in other processes related to cellular homeostasis, which are not d irectly associated with the damage response. ATM is the protein product of the gene mutated in the multi-system disorder ataxia-telangiectasia (AT), w hich is characterized by neuronal degeneration, immunodeficiency, chromosom al instability and cancer predisposition. The AT phenotype and the function s of the ATM protein revealed to date demonstrate the exceptionally multifa ceted nature of this protein.