Abstract
Mutants of the Saccharomyces cerevisiae ataxia telangiectasia mutated (ATM) homolog MEC1/SAD3/ESR1 were identified that could live only if the RAD53/SAD1 checkpoint kinase was overproduced. MEC1 and a structurally related gene, TEL1, have overlapping functions in response to DNA damage and replication blocks that in mutants can be provided by overproduction of RAD53. Both MEC1 and TEL1 were found to control phosphorylation of Rad53p in response to DNA damage. These results indicate that RAD53 is a signal transducer in the DNA damage and replication checkpoint pathways and functions downstream of two members of the ATM lipid kinase family. Because several members of this pathway are conserved among eukaryotes, it is likely that a RAD53-related kinase will function downstream of the human ATM gene product and play an important role in the mammalian response to DNA damage.
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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Ataxia Telangiectasia Mutated Proteins
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Base Sequence
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Cell Cycle Proteins*
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Cell Cycle*
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Checkpoint Kinase 2
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DNA Damage*
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DNA Replication
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DNA-Binding Proteins
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Fungal Proteins / genetics*
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Fungal Proteins / metabolism
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Gene Expression Regulation, Fungal
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Genes, Fungal*
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Intracellular Signaling Peptides and Proteins
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Molecular Sequence Data
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Mutation
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Phosphorylation
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Protein Kinases / genetics*
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Protein Kinases / metabolism
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Protein Serine-Threonine Kinases*
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Proteins / genetics
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Proteins / metabolism
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Saccharomyces cerevisiae / cytology
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Saccharomyces cerevisiae / genetics*
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Saccharomyces cerevisiae / metabolism
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Saccharomyces cerevisiae Proteins*
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Signal Transduction
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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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Proteins
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Saccharomyces cerevisiae Proteins
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Tumor Suppressor Proteins
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Protein Kinases
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Checkpoint Kinase 2
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ATM protein, human
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Ataxia Telangiectasia Mutated Proteins
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MEC1 protein, S cerevisiae
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Protein Serine-Threonine Kinases
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RAD53 protein, S cerevisiae