A suppressor of two essential checkpoint genes identifies a novel protein that negatively affects dNTP pools.
In Saccharomyces cerevisiae, MEC1 and RAD53 are essential for cell growth and checkpoint function. Their essential role in growth can be bypassed by deletion of a novel gene, SML1, which functions after several genes whose overexpression also suppresses mec1 inviability. In addition, sml1 affects various cellular processes analogous to overproducing the large subunit of ribonucleotide reductase, RNR1. These include effects on mitochondrial biogenesis, on the DNA damage response, and on cell growth. Consistent with these observations, the levels of dNTP pools in sml1 delta strains are increased compared to wild-type. This effect is not due to an increase in RNR transcription. Finally, both in vivo and in vitro experiments show that Sml1 binds to Rnr1. We propose that Sml1 inhibits dNTP synthesis posttranslationally by binding directly to Rnr1 and that Mec1 and Rad53 are required to relieve this inhibition.
Department of Genetics and Development, Columbia University, College of Physicians and Surgeons, New York, New York 10032-2704, USA.
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Zhao
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Muller
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Rothstein
D000595:Amino Acid Sequence; D001483:Base Sequence; D018797:Cell Cycle Proteins; D064447:Checkpoint Kinase 2; D003001:Cloning, Molecular; D004249:DNA Damage; D017931:DNA Primers; D004260:DNA Repair; D003854:Deoxyribonucleotides / Q000378:metabolism*; D004791:Enzyme Inhibitors; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D020043:Genes, Essential; D005800:Genes, Fungal; D005804:Genes, Lethal; D005816:Genetic Complementation Test; D047908:Intracellular Signaling Peptides and Proteins; D008928:Mitochondria / Q000502:physiology; D008969:Molecular Sequence Data; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D012264:Ribonucleotide Reductases / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins
D018797:Cell Cycle Proteins; D017931:DNA Primers; D003854:Deoxyribonucleotides; D004791:Enzyme Inhibitors; D005656:Fungal Proteins; D047908:Intracellular Signaling Peptides and Proteins; C115052:SML1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D012264:Ribonucleotide Reductases; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C088937:MEC1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; C067022:RAD53 protein, S cerevisiae