Cited by 728DNA Repair MechanismsFungal and yeast genetics researchBiochemical and Molecular Research

A Suppressor of Two Essential Checkpoint Genes Identifies a Novel Protein that Negatively Affects dNTP Pools

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Zhao, Xiaolan, Muller, Eric G.D, Rothstein, Rodney·1998·Molecular Cell

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.

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Crossref · 10.1016/s1097-2765(00)80277-4

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Authors
Zhao, X., Muller, E. G. D., & Rothstein, R.
Affiliations
  • Columbia University (US)
  • University of Washington (US)
Corresponding author
Rothstein, Rodney
Venue
Molecular Cell
Publisher
Elsevier BV
Published
1998-09
Volume
2
Issue
3
Pages
329-340
ISSN
1097-2765 (ISSN-L)
OpenAlex
W2034206561
Cited by
728
References
54
Citations by year
2026: 5 · 2025: 16 · 2024: 12 · 2023: 14 · 2022: 17 · 2021: 22 · 2020: 20 · 2019: 26 · 2018: 24 · 2017: 38 · 2016: 29 · 2015: 33 · 2014: 26 · 2013: 47 · 2012: 29
FWCI
7.56
Type
journal article
Language
en
Open access
Locations
  • Molecular Cell (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
National Institute of General Medical Sciences (GM 50237)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
Keywords
RNR1, ribonucleotide reductase, dNTP pools, Mec1, Rad53, DNA damage checkpoint, mitochondrial biogenesis, DNA damage response, cell growth, Saccharomyces cerevisiae
MeSH terms
Amino Acid Sequence, Base Sequence, Cloning, Molecular, Deoxyribonucleotides, DNA Damage, DNA Repair, Enzyme Inhibitors, Fungal Proteins, Genes, Fungal, Genes, Lethal, Genetic Complementation Test, Mitochondria, Molecular Sequence Data, Protein Kinases, Ribonucleotide Reductases, Saccharomyces cerevisiae, Gene Expression Regulation, Fungal, Protein Serine-Threonine Kinases, Gene Deletion, DNA Primers, Cell Cycle Proteins, Genes, Essential, Saccharomyces cerevisiae Proteins, Intracellular Signaling Peptides and Proteins, Checkpoint Kinase 2

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