The yeast TEL1 gene partially substitutes for human ATM in suppressing hyperrecombination, radiation-induced apoptosis and telomere shortening in A-T cells.
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.
Fritz
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E
GSF, National Research Center for Environment and Health, Institute of Radiobiology, Neuherberg, Germany. efritz@gsf.de
Friedl
A A
AA
Zwacka
R M
RM
Eckardt-Schupp
F
F
Meyn
M S
MS
D017209:Apoptosis / Q000528:radiation effects*; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D002461:Cell Line, Transformed; D004268:DNA-Binding Proteins; D005347:Fibroblasts; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology*; D005720:Gamma Rays; D005816:Genetic Complementation Test; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D016615:Telomere / Q000378:metabolism*; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism / Q000528:radiation effects; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D029701:Saccharomyces cerevisiae Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; C513623:TEL1 protein, S cerevisiae