Evidence map›Paper›PMID 30892639›Full record

ArticleNucleic acids research2019

Deoxyuridine in DNA has an inhibitory and promutagenic effect on RNA transcription by diverse RNA polymerases.

Junru Cui, Anthony Gizzi, James T Stivers

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.9field-weighted citation impact, top 26% 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

11 citing papers in PubMed, 16 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. (5'International journal of molecular sciences · 2021
    Article
  9. Review
  10. Deoxyuracil in DNA in health and disease.Current opinion in clinical nutrition and metabolic care · 2020
    Review
  11. 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

3 authors at 2 institutions in 1 country.

Junru CuiDepartment of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205-2185, USA.
Anthony GizziDepartment of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205-2185, USA.
James T StiversDepartment of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205-2185, USA.
Johns Hopkins Medicine · USJohns Hopkins University · US

Funding

BIOCHEMISTRY, CELLULAR AND MOLECULAR BIOLOGY PROGRAMT32GM007445 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI GREEN, RACHEL · 1985 to 2021
$24.1M
TRAINING IN AREAS FUNDAMENTAL TO CANCER RESEARCHT32CA009110 · NCI · JOHNS HOPKINS UNIVERSITY · PI MATUNIS, MICHAEL J., WEERARATNA, ASHANI T · 1985 to 2025
$13.1M
Fate of Invisible U/A Base Pairs Within HIV DNA in Myeloid Phagocytic CellsR01AI124777 · NIAID · JOHNS HOPKINS UNIVERSITY · PI STIVERS, JAMES T. · 2016 to 2020
$2.0M
Mechanism of Transcriptional Downregulation of HIV Gene Expression by U/A Base Pairs in Proviral DNAF32AI150561 · NIAID · JOHNS HOPKINS UNIVERSITY · PI GIZZI, ANTHONY · 2019 to 2020
$126k
NCI NIH HHS T32 CA009110NIAID NIH HHS F32 AI150561NIAID NIH HHS R01 AI124777NIGMS NIH HHS T32 GM007445
6 · The paper itself

Abstract

dUTP is a close structural congener of dTTP and can be readily incorporated into DNA opposite to adenine during DNA replication leading to non-mutagenic dU/A base pairs ('uracilation'). We find that dU/A pairs located within DNA transcriptional templates optimized for either T7 RNA polymerase (T7 RNAP) or human RNA polymerase II (pol II) have inhibitory and mutagenic effects on transcription. The data for T7 RNAP establishes that even a single dU/A pair can inhibit promoter binding and transcription initiation up to 30-fold, and that inhibitory effects on transcription elongation are also possible. Sequencing of the mRNA transcribed from uniformly uracilated DNA templates by T7 RNAP indicated an increased frequency of transversion and insertion mutations compared to all T/A templates. Strong effects of dU/A pairs on cellular transcription activity and fidelity were also observed with RNA pol II using uracil base excision repair (UBER)-deficient human cells. At the highest levels of template uracilation, transcription by RNA pol II was completely blocked. We propose that these effects arise from the decreased thermodynamic stability and increased dynamics of dU/A pairs in DNA. The potential implications of these findings on gene regulation and disease are discussed.

Indexed as

DNA RepairTranscription, GeneticBase PairingBase SequenceCell Line, TumorDeoxyuridineDNADNA-Directed RNA PolymerasesDNA ReplicationFibroblastsHumansKineticsMutationPromoter Regions, GeneticProtein BindingRNAbacteriophage T7 RNA polymeraseDeoxyuridineDNADNA-Directed RNA PolymerasesRNARNA Polymerase IIViral Proteins

Identifiers

PMID30892639
PMCPMC6486633
OpenAlexW2924271536

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.