REVIEW: Mechanisms of Non-canonical Activation of Ataxia Telangiectasia Mutated

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S. V. Khoronenkova^1,2

¹University of Cambridge, Department of Biochemistry, Cambridge CB2 1GA, UK; E-mail: sk870@cam.ac.uk

²Lomonosov Moscow State University, Department of Chemistry, 119991 Moscow, Russia

Received March 12, 2016

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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.

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KEY WORDS: ATM, Ataxia Telangiectasia mutated, DNA damage, DNA single-strand breaks, DNA double-strand breaks, R-loops

DOI: 10.1134/S0006297916130058

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