CHARACTERIZATION OF THE ATAXIA-TELANGIECTASIA GENE PRODUCT

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A-T is an autosomal recessive disorder characterized by oculocutaneous telangiectasias and progressive neuromotor dysfunction, cellular and humoral immune deficiencies, hypersensitivity to ionizing radiation and increased predisposition to leukemias and lymphomas. The 350 kD protein product resembles a phosphatidylinositol-3' kinase-like molecule but acts as a serine/threonine kinase.We have generated polyclonal antibodies against the ATM protein that led us to define the ATM protein as a predominantly nuclear protein that likely functions as a sensor for double-strand breaks in genomic DNA. More recent results involves dissecting the sequence motif responsible for nuclear targeting and in identifying the protein's role in p53-mediated apoptosis and cell cycle which indicates that there can be differential induction of Bax and p21 in the Atm null background. Atm apparently has no effect on p53-mediated activation of apoptosis as evidenced by Bax induction.