ATM

ATM (ataxia telangiectasia mutated) is a serine/threonine kinase activated by DNA double-strand breaks.

Function

ATM exists in the nucleus as an inactive dimer. A double-strand break - from ionizing radiation, replication fork collapse, or telomere dysfunction - exposes DNA ends, the MRN complex (MRE11-RAD50-NBS1) binds them, and ATM monomerizes and autophosphorylates into an active kinase. Active ATM phosphorylates hundreds of substrates, the central ones being p53 (stabilizing it and producing arrest or apoptosis), CHK2 (amplifying the signal), H2AX (marking the damage site for repair machinery), and BRCA1. The result is a coordinated program: arrest, repair, and - if repair fails - senescence or death.

In cancer

The gene