Cited by 114DNA Repair MechanismsBacterial Genetics and BiotechnologyDNA and Nucleic Acid Chemistry

Cost of rNTP/dNTP pool imbalance at the replication fork

Open access
Yao, Nina Y., Schroeder, Jeremy W., Yurieva, Olga, Simmons, Lyle A., O’Donnell, Mike E.·2013·Proceedings of the National Academy of Sciences

Abstract

The concentration of ribonucleoside triphosphates (rNTPs) in cells is far greater than the concentration of deoxyribonucleoside triphosphates (dNTPs), and this pool imbalance presents a challenge for DNA polymerases (Pols) to select their proper substrate. This report examines the effect of nucleotide pool imbalance on the rate and fidelity of the Escherichia coli replisome. We find that rNTPs decrease replication fork rate by competing with dNTPs at the active site of the C-family Pol III replicase at a step that does not require correct base-pairing. The effect of rNTPs on Pol rate generalizes to B-family eukaryotic replicases, Pols δ and ε. Imbalance of the dNTP pool also slows the replisome and thus is not specific to rNTPs. We observe a measurable frequency of rNMP incorporation that predicts one rNTP incorporated every 2.3 kb during chromosome replication. Given the frequency of rNMP incorporation, the repair of rNMPs is likely rapid. RNase HII nicks DNA at single rNMP residues to initiate replacement with dNMP. Considering that rNMPs will mark the new strand, RNase HII may direct strand-specificity for mismatch repair (MMR). How the newly synthesized strand is recognized for MMR is uncertain in eukaryotes and most bacteria, which lack a methyl-directed nicking system. Here we demonstrate that Bacillus subtilis incorporates rNMPs in vivo, that RNase HII plays a role in their removal, and the RNase HII gene deletion enhances mutagenesis, suggesting a possible role of incorporated rNMPs in MMR.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1073/pnas.1309506110

Cites

41 of 41 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Both replicative and translesion DNA polymerases make sugar errors.

    “Both replicative and translesion DNA polymerases make sugar errors”

    From Ribonucleotide errors, RNase HII, and ribonucleotide excision repair (2026) · cites this paper as Yao et al. 2013

    The paper’s introduction says DNA polymerases incorporate ribonucleotides at low frequency, and its results document this sugar error for the replicative polymerase Pol III. It does not specifically report that translesion polymerases make sugar errors; its reference to a family Y polymerase concerns discrimination against ribonucleotides. (LLM, conf=0.78)

    Experimental — accuracy not yet measured
  • rNMPs are the most common nucleotide requiring removal/repair from genomic DNA in organisms across all domains of life, owing in part to high rNTP:dNTP ratios and high incorporation rates.

    “rNMPs may represent the most common nucleotide requiring removal from genomic DNA in organisms spanning all domains of life”

    From Ribonucleotide errors, RNase HII, and ribonucleotide excision repair (2026) · cites this paper as Yao et al. 2013

    The introduction reports high cellular rNTP:dNTP ratios and abundant rNMP incorporation, and the Discussion says rNMPs are frequent in bacteria as well as yeast. The copy does not establish that rNMPs are the most common nucleotides requiring removal from DNA or extend that conclusion to all domains of life (pages not provided). (LLM, conf=0.83)

    Experimental — accuracy not yet measured
  • E. coli Pol III holoenzyme incorporates up to 2000 rNMPs per round of chromosomal replication in vitro.

    “it has been estimated that E. coli Pol III holoenzyme incorporates up to 2000 rNMPs per one round of chromosomal replication in vitro”

    From Ribonucleotide errors, RNase HII, and ribonucleotide excision repair (2026) · cites this paper as Yao et al. 2013

    The section headed “Incorporation of 2,000 rNMPs Predicted During Replication of the E. coli Genome” estimates about 2,000 rNMPs per daughter chromosome. That figure is extrapolated from in vitro selectivity measurements using in vivo nucleotide concentrations; the paper does not report an in vitro round of chromosomal replication incorporating up to 2,000 rNMPs. Page numbers are not provided in our copy. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

1 retracted

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Yao, N. Y., Schroeder, J. W., Yurieva, O., Simmons, L. A., & O’Donnell, M. E.
Affiliations
  • Rockefeller University (US)
  • University of Michigan (US)
  • Howard Hughes Medical Institute (US)
Venue
Proceedings of the National Academy of Sciences
Published
2013-07-23
Volume
110
Issue
32
Pages
12942-12947
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W1967720448
Cited by
114
References
41
Citations by year
2026: 5 · 2025: 4 · 2024: 7 · 2023: 10 · 2022: 8 · 2021: 8 · 2020: 4 · 2019: 13 · 2018: 8 · 2017: 10 · 2016: 8 · 2015: 11 · 2014: 17 · 2013: 1
FWCI
5.53
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Howard Hughes Medical Institute
  • National Institutes of Health
  • National Institute of General Medical Sciences (GM38831, T32GM007544, R01GM038839)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
Keywords
ribonucleoside triphosphates, DNA replication, DNA polymerase III, RNase HII, DNA mismatch repair, strand specificity, mutagenesis, Escherichia coli, Bacillus subtilis, DNA polymerase delta, DNA polymerase epsilon
MeSH terms
Bacillus subtilis, Binding, Competitive, Deoxyribonucleotides, DNA Polymerase III, DNA Repair, DNA Replication, DNA, Bacterial, Electrophoresis, Agar Gel, Escherichia coli, Models, Genetic, Mutation, Protein Binding, Ribonucleotides, Ribonuclease H, Escherichia coli Proteins

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review