Evidence map›Paper›PMID 25751426›Full record

ArticleNature structural & molecular biology2015

Evidence that processing of ribonucleotides in DNA by topoisomerase 1 is leading-strand specific.

Jessica S Williams, Anders R Clausen, Scott A Lujan, Lisette Marjavaara, Alan B Clark, Peter M Burgers, Andrei Chabes, Thomas A Kunkel

Abstract read
In one paragraph

Article in Nature structural & molecular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
3.9field-weighted citation impact, top 6% 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

37 citing papers in PubMed, 48 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Ribonucleotide incorporation into DNA during DNA replication and its consequences.Critical reviews in biochemistry and molecular biology · 2021
    Review
  8. Article
  9. Review
  10. Article
  11. Review
  12. Review
  13. Article
  14. Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
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

8 authors at 3 institutions in 2 countries.

Jessica S WilliamsGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA.
Anders R ClausenGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA.
Scott A LujanGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA.ORCID 0000000324008325
Lisette MarjavaaraDepartment of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
Alan B ClarkGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA.
Peter M BurgersDepartment of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri, USA.
Andrei Chabes1] Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden. [2] Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, Sweden.ORCID 0000000317088259
Thomas A KunkelGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA.
National Institutes of Health · USUmeå University · SEWashington University in St. Louis · 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
Molecular Genetics Support to Identify Gene/Environment Interactions in DiseaseZICES102546 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI GERRISH, KEVIN · 2009 to 2025
$30.5M
ENZYMOLOGY OF REPLICATION OF YEAST CHROMOSOMAL DNAR01GM032431 · NIGMS · WASHINGTON UNIVERSITY · PI BURGERS, PETER M · 1985 to 2015
$6.5M
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 ES065070NIGMS NIH HHS GM032431NIGMS NIH HHS R01 GM032431
6 · The paper itself

Abstract

Ribonucleotides incorporated during DNA replication are removed by RNase H2-dependent ribonucleotide excision repair (RER). In RER-defective yeast, topoisomerase 1 (Top1) incises DNA at unrepaired ribonucleotides, initiating their removal, but this is accompanied by RNA-DNA-damage phenotypes. Here we show that these phenotypes are incurred by a high level of ribonucleotides incorporated by a leading strand-replicase variant, DNA polymerase (Pol) ɛ, but not by orthologous variants of the lagging-strand replicases, Pols α or δ. Moreover, loss of both RNases H1 and H2 is lethal in combination with increased ribonucleotide incorporation by Pol ɛ but not by Pols α or δ. Several explanations for this asymmetry are considered, including the idea that Top1 incision at ribonucleotides relieves torsional stress in the nascent leading strand but not in the nascent lagging strand, in which preexisting nicks prevent the accumulation of superhelical tension.

Indexed as

DNADNA Polymerase IIDNA RepairDNA ReplicationDNA Topoisomerases, Type IRibonucleotidesSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsDNADNA Polymerase IIDNA Topoisomerases, Type IRibonucleotidesSaccharomyces cerevisiae Proteins

Identifiers

PMID25751426
PMCPMC4835660
OpenAlexW1966982053

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.