Evidence map›Paper›PMID 23882084›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2013

Cost of rNTP/dNTP pool imbalance at the replication fork.

Nina Y Yao, Jeremy W Schroeder, Olga Yurieva, Lyle A Simmons, Mike E O'Donnell

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
81citing papers in PubMed, 1 pooled it
5.5field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

81 citing papers in PubMed, 1 synthesis or guideline pooled it, 115 citations in OpenAlex.

  1. Synthetic lethal mutants inJournal of bacteriology · 2023
    Pooled it
  2. Article
  3. Ribonucleotide errors, RNase HII, and ribonucleotide excision repair.Critical reviews in biochemistry and molecular biology · 2026
    Review
  4. Article
  5. Review
  6. DNA polymerase I: structure, activity, and function in bacterial DNA replication and repair.Critical reviews in biochemistry and molecular biology · 2026
    Review
  7. Article
  8. Article
  9. Article
  10. bioRxiv : the preprint server for biology · 2025
    Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Review
  16. Article
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  19. Article
  20. Article

21 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 1 country.

Nina Y YaoThe Rockefeller University, New York, NY 10065, USA.
Jeremy W Schroeder
Olga Yurieva
Lyle A Simmons
Mike E O'Donnell
Rockefeller University · USUniversity of Michigan–Ann Arbor · USHoward Hughes Medical Institute · US

Funding

PREDOCTORAL TRAINING IN GENETICST32GM007544 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MORAN, JOHN V. · 1985 to 2022
$11.3M
BIOCHEMICAL MECHANISM OF DNA POLYMERASE III HOLOENZYMER01GM038839 · NIGMS · WEILL MEDICAL COLLEGE OF CORNELL UNIV · PI O'DONNELL, MICHAEL E · 1988 to 2014
$2.9M
Howard Hughes Medical InstituteNIGMS NIH HHS GM38831NIGMS NIH HHS R01 GM038839NIGMS NIH HHS T32 GM007544NIGMS NIH HHS T32GM007544
6 · The paper itself

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.

Indexed as

DNA ReplicationBacillus subtilisBinding, CompetitiveDeoxyribonucleotidesDNA, BacterialDNA Polymerase IIIDNA RepairElectrophoresis, Agar GelEscherichia coliEscherichia coli ProteinsModels, GeneticMutationProtein BindingRibonuclease HRibonucleotidesDeoxyribonucleotidesDNA, BacterialDNA Polymerase IIIEscherichia coli ProteinsRibonuclease Hribonuclease HIIRibonucleotides

Identifiers

PMID23882084
PMCPMC3740908
OpenAlexW1967720448

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.