Evidence map›Paper›PMID 28717002›Full record

ArticleThe Journal of biological chemistry2017

Human ribonuclease H1 resolves R-loops and thereby enables progression of the DNA replication fork.

Shankar Parajuli, Daniel C Teasley, Bhavna Murali, Jessica Jackson, Alessandro Vindigni, Sheila A Stewart

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
2.7field-weighted citation impact, top 9% 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

51 citing papers in PubMed, 70 citations in OpenAlex.

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  11. AAV-mediated genome editing is influenced by the formation of R-loops.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Article
  12. Article
  13. Article
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  15. AAV-mediated genome editing is influenced by the formation of R-loops.bioRxiv : the preprint server for biology · 2024
    Article
  16. Review
  17. Review
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  19. Article
  20. p53-dependent R-loop formation and HPV pathogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2023
    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

6 authors at 3 institutions in 1 country.

Shankar ParajuliFrom the Departments of Cell Biology and Physiology and.
Daniel C TeasleyFrom the Departments of Cell Biology and Physiology and.
Bhavna MuraliFrom the Departments of Cell Biology and Physiology and.
Jessica Jacksonthe Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, Missouri 63104.
Alessandro Vindignithe Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, Missouri 63104 avindign@slu.edu.
Sheila A StewartFrom the Departments of Cell Biology and Physiology and sheila.stewart@wustl.edu.
Saint Louis University · USUniversity Hospitals Seidman Cancer Center · USWashington University in St. Louis · US

Funding

MOLECULAR ONCOLOGY TRAINING GRANTT32CA113275 · NCI · WASHINGTON UNIVERSITY · PI Matthew J Walter · 2006 to 2026
$5.7M
New Mechanisms of Replication Stress ResponseR01GM108648 · NIGMS · SAINT LOUIS UNIVERSITY · PI VINDIGNI, ALESSANDRO · 2014 to 2018
$1.4M
THE ROLE OF FIBROBLAST-DERIVED OSTEOPONTIN IN TUMORIGENESISR01CA130919 · NCI · WASHINGTON UNIVERSITY · PI STEWART, SHEILA A · 2009 to 2013
$1.2M
NCI NIH HHS R01 CA130919NCI NIH HHS T32 CA113275NIGMS NIH HHS R01 GM108648
6 · The paper itself

Abstract

Faithful DNA replication is essential for genome stability. To ensure accurate replication, numerous complex and redundant replication and repair mechanisms function in tandem with the core replication proteins to ensure DNA replication continues even when replication challenges are present that could impede progression of the replication fork. A unique topological challenge to the replication machinery is posed by RNA-DNA hybrids, commonly referred to as R-loops. Although R-loops play important roles in gene expression and recombination at immunoglobulin sites, their persistence is thought to interfere with DNA replication by slowing or impeding replication fork progression. Therefore, it is of interest to identify DNA-associated enzymes that help resolve replication-impeding R-loops. Here, using DNA fiber analysis, we demonstrate that human ribonuclease H1 (RNH1) plays an important role in replication fork movement in the mammalian nucleus by resolving R-loops. We found that RNH1 depletion results in accumulation of RNA-DNA hybrids, slowing of replication forks, and increased DNA damage. Our data uncovered a role for RNH1 in global DNA replication in the mammalian nucleus. Because accumulation of RNA-DNA hybrids is linked to various human cancers and neurodegenerative disorders, our study raises the possibility that replication fork progression might be impeded, adding to increased genomic instability and contributing to disease.

Indexed as

DNA ReplicationReplication OriginAmino Acid SubstitutionChromosome PositioningDNADNA DamageDNA Replication TimingGene Expression RegulationGenomic InstabilityGreen Fluorescent ProteinsHEK293 CellsHumansIn Situ Hybridization, FluorescenceMutationNucleic Acid ConformationNucleic Acid HybridizationDNAGreen Fluorescent ProteinsRecombinant Fusion ProteinsRibonuclease Hribonuclease HIRNARNA, Messengercancercancer biologychromosomesDNA repairDNA replication

Identifiers

PMID28717002
PMCPMC5602383
OpenAlexW2735341248

What OpenQuestion holds

Textmetadata
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.