Evidence map›Paper›PMID 20729855›Full record

ArticleNature chemical biology2010

Genome instability due to ribonucleotide incorporation into DNA.

Stephanie A Nick McElhinny, Dinesh Kumar, Alan B Clark, Danielle L Watt, Brian E Watts, Else-Britt Lundström, Erik Johansson, Andrei Chabes, Thomas A Kunkel

Open access · greenAbstract read
In one paragraph

Article in Nature chemical biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 275 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
275citing papers in PubMed, 1 pooled it
12.2field-weighted citation impact, top 1% 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

275 citing papers in PubMed, 1 synthesis or guideline pooled it, 392 citations in OpenAlex.

  1. Synthetic lethal mutants inJournal of bacteriology · 2023
    Pooled it
  2. Article
  3. Article
  4. Article
  5. Ribonucleotide errors, RNase HII, and ribonucleotide excision repair.Critical reviews in biochemistry and molecular biology · 2026
    Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. bioRxiv : the preprint server for biology · 2025
    Article
  18. The relevance of RNA-DNA interactions as regulators of physiological functions.Pflugers Archiv : European journal of physiology · 2025
    Review
  19. Article
  20. RRM2B deficiency causes dATP and dGTP depletion through enhanced degradation and slower synthesis.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article

215 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

9 authors at 3 institutions in 2 countries.

Stephanie A Nick McElhinnyLaboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA.
Dinesh Kumar
Alan B Clark
Danielle L Watt
Brian E Watts
Else-Britt Lundström
Erik Johansson
Andrei Chabes
Thomas A Kunkel
National Institutes of Health · USUmeå University · SENational Institute of Environmental Health Sciences · US

Funding

Structure-Function Studies Of DNA Replication FidelityZIAES065070 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI KUNKEL, THOMAS A · 2009 to 2025
$30.6M
Structure-Function Studies Of DNA Replication FidelityZ01ES065070 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI KUNKEL, THOMAS A · 1991 to 2008
$4.3M
Intramural NIH HHS Z01 ES065070
6 · The paper itself

Abstract

Maintaining the chemical identity of DNA depends on ribonucleotide exclusion by DNA polymerases. However, ribonucleotide exclusion during DNA synthesis in vitro is imperfect. To determine whether ribonucleotides are incorporated during DNA replication in vivo, we substituted leucine or glycine for an active-site methionine in yeast DNA polymerase ϵ (Pol ϵ). Ribonucleotide incorporation in vitro was three-fold lower for M644L and 11-fold higher for M644G Pol ϵ compared to wild-type Pol ϵ. This hierarchy was recapitulated in vivo in yeast strains lacking RNase H2. Moreover, the pol2-M644G rnh201Δ strain progressed more slowly through S phase, had elevated dNTP pools and generated 2-5-base-pair deletions in repetitive sequences at a high rate and in a gene orientation-dependent manner. The data indicate that ribonucleotides are incorporated during replication in vivo, that they are removed by RNase H2-dependent repair and that defective repair results in replicative stress and genome instability via DNA strand misalignment.

Indexed as

Genomic InstabilityBase SequenceDNA-Directed DNA PolymeraseDNA, FungalDNA ReplicationGenome, FungalMolecular Sequence DataMutagenesisMutationPhenotypeRibonuclease HRibonucleotidesSaccharomyces cerevisiaeTemplates, GeneticDNA-Directed DNA PolymeraseDNA, FungalRibonuclease Hribonuclease HIIRibonucleotides

Identifiers

PMID20729855
PMCPMC2942972
OpenAlexW2078507463

What OpenQuestion holds

Textmetadata
LicenceTDM
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.