Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Apoptosis / radiation effects*
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Ataxia Telangiectasia Mutated Proteins
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Cell Cycle Proteins
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Cell Line, Transformed
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DNA-Binding Proteins
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Fibroblasts
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Fungal Proteins / genetics
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Fungal Proteins / physiology*
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Gamma Rays
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Genetic Complementation Test
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Humans
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Intracellular Signaling Peptides and Proteins
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Mutation
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / physiology*
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Recombination, Genetic*
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Saccharomyces cerevisiae
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Saccharomyces cerevisiae Proteins
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Telomere / metabolism*
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Transfection
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Tumor Suppressor Protein p53 / metabolism
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Tumor Suppressor Protein p53 / radiation effects
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Tumor Suppressor Proteins
Substances
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Cell Cycle Proteins
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DNA-Binding Proteins
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Fungal Proteins
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Intracellular Signaling Peptides and Proteins
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Saccharomyces cerevisiae Proteins
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Tumor Suppressor Protein p53
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Tumor Suppressor Proteins
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ATM protein, human
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Ataxia Telangiectasia Mutated Proteins
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Protein Serine-Threonine Kinases
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TEL1 protein, S cerevisiae