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Biochemistry (Moscow)

, Volume 81, Issue 13, pp 1669–1675 | Cite as

Mechanisms of non-canonical activation of ataxia telangiectasia mutated

  • S. V. KhoronenkovaEmail author
Review

Abstract

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.

Keywords

ATM Ataxia Telangiectasia mutated DNA damage DNA single-strand breaks DNA double-strand breaks R-loops 

Abbreviations

А-Т

Ataxia Telangiectasia

АТМ

Ataxia Telangiectasia mutated

ATR

АТМ- and Rad3-related kinase

DNA-PKcs

DNA-dependent protein kinase catalytic subunit

DSB

DNA double-strand break

MRN

Mre11-Rad50-Nbs1 complex

R-loop

RNA–DNA hybrid

SSB

DNA single-strand break

Top1

DNA topoisomerase I

Top1cc

Top1–DNA intermediate

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Copyright information

© Pleiades Publishing, Ltd. 2016

Authors and Affiliations

  1. 1.Department of BiochemistryUniversity of CambridgeCambridgeUK
  2. 2.Department of ChemistryLomonosov Moscow State UniversityMoscowRussia

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