ATAXIA-TELANGIECTASIA - IS ATM A SENSOR OF OXIDATIVE DAMAGE AND STRESS

Ataxia-telangiectasia (A-T) is a pleiotropic recessive disorder charac terized by cerebellar ataxia, immunodeficiency, specific developmental defects, profound predisposition to cancer and acute radiosensitivity . Functional inactivation of a single gene product, ATM, accounts for this compound phenotype. We suggest that ATM acts as a sensor of react ive oxygen species and/or oxidative damage of cellular macromolecules, including DNA. In turn, ATM induces signalling through multiple pathw ays, 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 oc cur under normal physiological conditions, ultimately leading to apopt osis of particularly sensitive cells, such as neurons and thymocytes.