Abstract
RAD53 and MEC1 are essential Saccharomyces cerevisiae genes required for the DNA replication and DNA damage checkpoint responses. Their lethality can be suppressed by increasing the intracellular pool of deoxynucleotide triphosphates. We report that deletion of YKU70 or YKU80 suppresses mec1Delta, but not rad53Delta, lethality. We show that suppression of mec1Delta lethality is not due to Ku--associated telomeric defects but rather results from the inability of Ku- cells to efficiently repair DNA double strand breaks by nonhomologous end joining. Consistent with these results, mec1Delta lethality is also suppressed by lif1Delta, which like yku70Delta and yku80Delta, prevents nonhomologous end joining. The viability of yku70Delta mec1Delta and yku80Delta mec1Delta cells depends on the ATM-related Tel1 kinase, the Mre11-Rad50-Xrs2 complex, and the DNA damage checkpoint protein Rad9. We further report that this Mec1-independent pathway converges with the Rad53/Dun1-regulated checkpoint kinase cascade and leads to the degradation of the ribonucleotide reductase inhibitor Sml1.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Cell Cycle
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism
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Cell Death
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Checkpoint Kinase 2
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Endodeoxyribonucleases / genetics
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Endodeoxyribonucleases / metabolism*
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Exodeoxyribonucleases / genetics
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Exodeoxyribonucleases / metabolism*
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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, Lethal / genetics
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Intracellular Signaling Peptides and Proteins
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Protein Binding
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Protein Kinases / genetics
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Protein Kinases / metabolism
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism
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RNA, Messenger / genetics
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Ribonucleotide Reductases / antagonists & inhibitors
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Ribonucleotide Reductases / 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 / genetics
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Saccharomyces cerevisiae Proteins / metabolism*
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Signal Transduction*
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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RNA, Messenger
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SML1 protein, S cerevisiae
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Saccharomyces cerevisiae Proteins
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YKU70 protein, S cerevisiae
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YKU80 protein, S cerevisiae
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high affinity DNA-binding factor, S cerevisiae
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Ribonucleotide Reductases
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Protein Kinases
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DUN1 protein, S cerevisiae
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Checkpoint Kinase 2
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MEC1 protein, S cerevisiae
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Protein Serine-Threonine Kinases
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TEL1 protein, S cerevisiae
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RAD53 protein, S cerevisiae
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Endodeoxyribonucleases
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Exodeoxyribonucleases
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MRE11 protein, S cerevisiae