Vol. 11, Issue 8, 2605-2616, August 2000

The Yeast TEL1 Gene Partially Substitutes for Human ATM in Suppressing Hyperrecombination, Radiation-Induced Apoptosis and Telomere Shortening in A-T Cells

Eberhard Fritz,^* Anna A. Friedl, Ralf M. Zwacka, Friederike Eckardt-Schupp,^* and M. Stephen Meyn^§

 ^*GSF, National Research Center for Environment and Health, Institute of Radiobiology, 85758 Neuherberg, Germany  Department of Radiobiology, University of Munich, 80336 Munich, Germany  University of Edinburgh, Department of Oncology, Edinburgh, United Kingdom  ^§The Hospital for Sick Children, Toronto M5G 1X8, Canada

Homozygous mutations in the human ATM gene lead to a pleiotropic clinical phenotype of ataxia-telangiectasia (A-T) patients and correlating cellular deficiencies in cells derived from A-T donors. Saccharomyces cerevisiae tel1 mutants lacking Tel1p, which is the closest sequence homologue to the ATM protein, share some of the cellular defects with A-T. Through genetic complementation of A-T cells with the yeast TEL1 gene, we provide evidence that Tel1p can partially compensate for ATM in suppressing hyperrecombination, radiation-induced apoptosis, and telomere shortening. Complementation appears to be independent of p53 activation. The data provided suggest that TEL1 is a functional homologue of human ATM in yeast, and they help to elucidate different cellular and biochemical pathways in human cells regulated by the ATM protein.