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Hypothesis: Ataxia‐telangiectasia: Is ATM a sensor of oxidative damage and stress?
Author(s) -
Rotman Galit,
Shiloh Yosef
Publication year - 1997
Publication title -
bioessays
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.175
H-Index - 184
eISSN - 1521-1878
pISSN - 0265-9247
DOI - 10.1002/bies.950191011
Subject(s) - ataxia telangiectasia , dna damage , oxidative stress , reactive oxygen species , microbiology and biotechnology , phenotype , biology , apoptosis , oxidative phosphorylation , cancer research , dna repair , genetics , gene , dna , biochemistry
Ataxia‐telangiectasia (A‐T) is a pleiotropic recessive disorder characterized cerebellar ataxia, immunodeficiency, specific developmental defects, profound predisposition to cancer and acute radiosensitivity. Functional inactivation of single gene product, ATM, accounts for this compound phenotype. We suggest that ATM acts as a sensor of reactive oxygen species and/or oxidative damage cellular macromolecules, including DNA. In turn, ATM induces signalling through multiple pathways, thereby coordinating acute phase stress responses with cell cycle checkpoint control and repair of oxidative damage. Absence of ATM is proposed to limit the repair of insidious oxidative damage that can occur under normal physiological conditions, ultimately leading to apoptosis of particularly sensitive cells, such as neurons and thymocytes.