Evidence map›Paper›PMID 22579044›Full record

ArticleCell2012

Enzymatic removal of ribonucleotides from DNA is essential for mammalian genome integrity and development.

Martin A M Reijns, Björn Rabe, Rachel E Rigby, Pleasantine Mill, Katy R Astell, Laura A Lettice, Shelagh Boyle, Andrea Leitch, Margaret Keighren, Fiona Kilanowski and 9 more

Open access · hybridAbstract read
In one paragraph

Article in Cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 311 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
311citing papers in PubMed, 1 pooled it
18.0field-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

311 citing papers in PubMed, 1 synthesis or guideline pooled it, 457 citations in OpenAlex.

  1. Synthetic lethal mutants inJournal of bacteriology · 2023
    Pooled it
  2. RNASEH2B loss and PARP inhibition in advanced prostate cancer.The Journal of clinical investigation · 2024
    Trial
  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. HeterozygousiScience · 2026
    Article
  9. Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Action-at-a-distance mutations by 8-oxo-7,8-dihydroguanine: adenine pair triggered by MUTYH.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2025
    Article
  17. Review
  18. Article
  19. The relevance of RNA-DNA interactions as regulators of physiological functions.Pflugers Archiv : European journal of physiology · 2025
    Review
  20. Article

251 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

19 authors at 3 institutions in 1 country.

Martin A M ReijnsMedical Research Council Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
Björn Rabe
Rachel E Rigby
Pleasantine Mill
Katy R Astell
Laura A Lettice
Shelagh Boyle
Andrea Leitch
Margaret Keighren
Fiona Kilanowski
Paul S Devenney
David Sexton
Graeme Grimes
Ian J Holt
Robert E Hill
Martin S Taylor
Kirstie A Lawson
Julia R Dorin
Andrew P Jackson
Medical Research Council · GBMRC Institute of Genetics and Molecular Medicine · GBUniversity of Edinburgh · GB

Funding

Medical Research Council MC_PC_U127580972Medical Research Council MC_PC_U127597124Medical Research Council MC_U105663140Medical Research Council MC_U127584494Medical Research Council MC_U127597124Wellcome Trust
6 · The paper itself

Abstract

The presence of ribonucleotides in genomic DNA is undesirable given their increased susceptibility to hydrolysis. Ribonuclease (RNase) H enzymes that recognize and process such embedded ribonucleotides are present in all domains of life. However, in unicellular organisms such as budding yeast, they are not required for viability or even efficient cellular proliferation, while in humans, RNase H2 hypomorphic mutations cause the neuroinflammatory disorder Aicardi-Goutières syndrome. Here, we report that RNase H2 is an essential enzyme in mice, required for embryonic growth from gastrulation onward. RNase H2 null embryos accumulate large numbers of single (or di-) ribonucleotides embedded in their genomic DNA (>1,000,000 per cell), resulting in genome instability and a p53-dependent DNA-damage response. Our findings establish RNase H2 as a key mammalian genome surveillance enzyme required for ribonucleotide removal and demonstrate that ribonucleotides are the most commonly occurring endogenous nucleotide base lesion in replicating cells.

Indexed as

DNA ReplicationAnimalsChromosomal InstabilityDNA-Directed DNA PolymeraseEmbryo, MammalianEmbryonic Stem CellsFemaleMaleMiceMice, Inbred C57BLRibonuclease HRibonucleotidesTumor Suppressor Protein p53DNA-Directed DNA PolymeraseRibonuclease HRibonucleotidesTumor Suppressor Protein p53

Identifiers

PMID22579044
PMCPMC3383994
OpenAlexW2139039510

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.