Evidence map›Paper›PMID 37611058›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2023

p53-dependent R-loop formation and HPV pathogenesis.

Conor Winslow Templeton, Laimonis A Laimins

Open access · hybridAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
7.3field-weighted citation impact, top 2% 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

32 citing papers in PubMed, 34 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Differential roles of type I topoisomerases in regulating HPV pathogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. Viral oncogenesis in cancer: from mechanisms to therapeutics.Signal transduction and targeted therapy · 2025
    Review
  16. Article
  17. Review
  18. p53 activates circASCC3 to repress R-loops and enhance resistance to chemotherapy.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  19. Review
  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

2 authors at 1 institution in 1 country.

Conor Winslow TempletonDepartment of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611.
Laimonis A LaiminsDepartment of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611.ORCID 0000-0002-6314-623X
Northwestern University · US

Funding

Tumor Environment and Metastasis (TEAM) Research ProgramP30CA060553 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Devalingam Mahalingam · 1993 to 2026
$153.9M
REGULATION OF HUMAN PAPILLOMAVIRUS GENE EXPRESSIONR01CA059655 · NCI · UNIVERSITY OF CHICAGO · PI LAIMINS, LAIMONIS A. · 1993 to 2023
$7.4M
The Role of Keratinocytes as Independent ThermosensorsP30AR057216 · NIAMS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI BUDUNOVA, IRINA · 2009 to 2018
$6.0M
Renewal: HPV and the DNA Damage ResponseR01CA142861 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Laimonis A. LAIMINS · 2010 to 2026
$5.2M
Post Graduate Program in Cutaneous BiologyT32AR060710 · NIAMS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Amy S Paller · 2012 to 2026
$2.4M
NCI NIH HHS P30 CA060553NCI NIH HHS R01 CA059655NCI NIH HHS R01 CA142861NIAMS NIH HHS P30 AR057216NIAMS NIH HHS T32 AR060710
6 · The paper itself

Abstract

R-loops are trimeric RNA: DNA hybrids that are important physiological regulators of transcription; however, their aberrant formation or turnover leads to genomic instability and DNA breaks. High-risk human papillomaviruses (HPV) are the causative agents of genital as well as oropharyngeal cancers and exhibit enhanced amounts of DNA breaks. The levels of R-loops were found to be increased up to 50-fold in cells that maintain high-risk HPV genomes and were readily detected in squamous cell cervical carcinomas in vivo but not in normal cells. The high levels of R-loops in HPV-positive cells were present on both viral and cellular sites together with RNase H1, an enzyme that controls their resolution. Depletion of RNase H1 in HPV-positive cells further increased R-loop levels, resulting in impaired viral transcription and replication along with reduced expression of the DNA repair genes such as FANCD2 and ATR, both of which are necessary for viral functions. Overexpression of RNase H1 decreased total R-loop levels, resulting in a reduction of DNA breaks by over 50%. Furthermore, increased RNase H1 expression blocked viral transcription and replication while enhancing the expression of factors in the innate immune regulatory pathway. This suggests that maintaining elevated R-loop levels is important for the HPV life cycle. The E6 viral oncoprotein was found to be responsible for inducing high levels of R-loops by inhibiting p53's transcriptional activity. Our studies indicate that high R-loop levels are critical for HPV pathogenesis and that this depends on suppressing the p53 pathway.

Indexed as

Carcinoma, Squamous CellFanconi AnemiaPapillomavirus InfectionsHumansR-Loop StructuresTumor Suppressor Protein p53Tumor Suppressor Protein p53HPVlife cyclep53R-loops

Identifiers

PMID37611058
PMCPMC10467572
OpenAlexW4386090787

What Socratic 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 Socratic graph.