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Cited by 151DNA Repair MechanismsFungal and yeast genetics researchBiochemical and Molecular Research

Subcellular localization of yeast ribonucleotide reductase regulated by the DNA replication and damage checkpoint pathways

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Yao, Ruojin, Zhang, Zhen, An, Xiuxiang, Bucci, Brigid, Perlstein, Deborah L., Stubbe, JoAnne, Huang, Mingxia·2003·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1131932100PMC PMC164498
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Abstract

The fidelity of DNA replication and repair processes is critical for maintenance of genomic stability. Ribonucleotide reductase (RNR) catalyzes the rate-limiting step in dNTP production and thus plays an essential role in DNA synthesis. The level and activity of RNR are highly regulated by the cell cycle and DNA damage checkpoints, which maintain optimal dNTP pools required for genetic fidelity. RNRs are composed of a large subunit that binds the nucleoside diphosphate substrates and allosteric effectors and a small subunit that houses the di-iron tyrosyl radical cofactor essential for the reduction process. In Saccharomyces cerevisiae , there are two large subunits (Rnr1 and Rnr3) and two small subunits (Rnr2 and Rnr4). Here we report the subcellular localization of Rnr1–4 during normal cell growth and the redistribution of Rnr2 and Rnr4 in response to DNA damage and replicational stress. During the normal cell cycle, Rnr1 and Rnr3 are predominantly localized to the cytoplasm and Rnr2 and Rnr4 are predominantly present in the nucleus. Under genotoxic stress, Rnr2 and Rnr4 become redistributed to the cytoplasm in a checkpoint-dependent manner. Subcellular redistribution of Rnr2 and Rnr4 can occur in the absence of the transcriptional induction of the RNR genes after DNA damage and likely represents a posttranslational event. These results suggest a mechanism by which DNA damage checkpoint modulates RNR activity through the temporal and spatial regulation of its subunits.

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  • Checkpoints actively stimulate repair processes and, in higher eukaryotes, trigger apoptosis when damage cannot be successfully dealt with.

    “The checkpoints also actively stimulate the repair processes [1–9] and, in higher eukaryotes, trigger the apoptotic response, if damage cannot be dealt with successfully [10–12].”

    From Mind the gap: keeping UV lesions in check (2011) · cites this paper as [2]

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Authors
Yao, R., Zhang, Z., An, X., Bucci, B., Perlstein, D. L., Stubbe, J., & Huang, M.
Affiliations
  • University of Colorado Health (US)
  • Massachusetts Institute of Technology (US)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2003-05-05
Volume
100
Issue
11
Pages
6628-6633
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.1131932100
PMC
PMC164498
OpenAlex
W2162031449
Cited by
151
References
56
Citations by year
2026: 2 · 2024: 3 · 2022: 3 · 2021: 2 · 2020: 3 · 2019: 4 · 2018: 3 · 2017: 11 · 2016: 6 · 2015: 10 · 2014: 8 · 2013: 7 · 2012: 10
FWCI
3.22
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (GM29595)
  • National Cancer Institute (T32CA009112, CA 095207, R01CA095207, T32 CA09112-27)
  • National Institute of General Medical Sciences (GM29595, R01GM029595)
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
ribonucleotide reductase, subcellular localization, DNA damage checkpoint, DNA replication checkpoint, Saccharomyces cerevisiae, RNR1, post-translational regulation, dNTP pools, genome stability, genotoxic stress, cell cycle regulation
MeSH terms
DNA Damage, DNA Replication, Ribonucleotide Reductases, Saccharomyces cerevisiae, Subcellular Fractions, Transcription, Genetic, Fluorescent Antibody Technique, Indirect

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