2Lomonosov Moscow State University, Department of Chemistry, 119991 Moscow, Russia
Received March 12, 2016
ATM is a master regulator of the cellular response to DNA damage. The classical mechanism of ATM activation involves its monomerization in response to DNA double-strand breaks, resulting in ATM-dependent phosphorylation of more than a thousand substrates required for cell cycle progression, DNA repair, and apoptosis. Here, new experimental evidence for non-canonical mechanisms of ATM activation in response to stimuli distinct from DNA double-strand breaks is discussed. It includes cytoskeletal changes, chromatin modifications, RNA–DNA hybrids, and DNA single-strand breaks. Noncanonical ATM activation may be important for the pathology of the multisystemic disease Ataxia Telangiectasia.
KEY WORDS: ATM, Ataxia Telangiectasia mutated, DNA damage, DNA single-strand breaks, DNA double-strand breaks, R-loops