A suppressor of two essential checkpoint genes identifies a novel protein that negatively affects dNTP pools

Mol Cell. 1998 Sep;2(3):329-40. doi: 10.1016/s1097-2765(00)80277-4.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Cell Cycle Proteins*
  • Checkpoint Kinase 2
  • Cloning, Molecular
  • DNA Damage
  • DNA Primers
  • DNA Repair
  • Deoxyribonucleotides / metabolism*
  • Enzyme Inhibitors*
  • Fungal Proteins / genetics*
  • Fungal Proteins / metabolism
  • Gene Deletion
  • Gene Expression Regulation, Fungal
  • Genes, Essential
  • Genes, Fungal*
  • Genes, Lethal
  • Genetic Complementation Test
  • Intracellular Signaling Peptides and Proteins
  • Mitochondria / physiology
  • Molecular Sequence Data
  • Protein Kinases / genetics
  • Protein Kinases / metabolism
  • Protein-Serine-Threonine Kinases*
  • Ribonucleotide Reductases / genetics
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins*

Substances

  • Cell Cycle Proteins
  • DNA Primers
  • Deoxyribonucleotides
  • Enzyme Inhibitors
  • Fungal Proteins
  • Intracellular Signaling Peptides and Proteins
  • SML1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Ribonucleotide Reductases
  • Protein Kinases
  • Checkpoint Kinase 2
  • MEC1 protein, S cerevisiae
  • Protein-Serine-Threonine Kinases
  • RAD53 protein, S cerevisiae