Evidence map›Paper›PMID 38719805›Full record

ArticleNature communications2024

Identification and characterization of small molecule inhibitors of the LINE-1 retrotransposon endonuclease.

Alexandra M D'Ordine, Gerwald Jogl, John M Sedivy

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
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

8 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Approaches to repurposing reverse transcriptase antivirals in cancer.British journal of clinical pharmacology · 2025
    Review
  5. HELQ Maintains Genome Stability of Primordial Germ Cells by Inhibiting LINE-1 Expression.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  6. Review
  7. Article
  8. Review
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.

Alexandra M D'OrdineDepartment of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI, USA.ORCID http://orcid.org/0000-0003-0553-2615
Gerwald JoglDepartment of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI, USA. gerwald_jogl@brown.edu.ORCID http://orcid.org/0000-0002-5465-5315
John M SedivyDepartment of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI, USA. john_sedivy@brown.edu.ORCID http://orcid.org/0000-0001-9363-4253

Funding

X-ray Scattering Technology CoreP30GM133893 · NIGMS · BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB · PI Vivian Stojanoff · 2019 to 2026
$38.6M
Somatic Activation of Retrotransposition: A New Molecular Mechanism of Aging?P01AG051449 · NIA · BROWN UNIVERSITY · PI John M Sedivy · 2016 to 2026
$30.4M
TRAINING IN MOLECULAR &CELL BIOLOGY &BIOCHEMISTRYT32GM007601 · NIGMS · BROWN UNIVERSITY · PI MOWRY, KIMBERLY L. · 1985 to 2019
$6.4M
MECHANISMS OF REPLICATIVE SENESCENCE IN CELLSR01AG016694 · NIA · BROWN UNIVERSITY · PI SEDIVY, JOHN M · 1999 to 2024
$5.7M
Effectors of cellular senescence statesR37AG016694 · NIA · BROWN UNIVERSITY · PI SEDIVY, JOHN M · 2009 to 2018
$3.2M
NIA NIH HHS P01 AG051449NIA NIH HHS R01 AG016694NIA NIH HHS R37 AG016694NIGMS NIH HHS P30 GM133893NIGMS NIH HHS T32 GM007601
6 · The paper itself

Abstract

The long interspersed nuclear element-1 (LINE-1 or L1) retrotransposon is the only active autonomously replicating retrotransposon in the human genome. L1 harms the cell by inserting new copies, generating DNA damage, and triggering inflammation. Therefore, L1 inhibition could be used to treat many diseases associated with these processes. Previous research has focused on inhibition of the L1 reverse transcriptase due to the prevalence of well-characterized inhibitors of related viral enzymes. Here we present the L1 endonuclease as another target for reducing L1 activity. We characterize structurally diverse small molecule endonuclease inhibitors using computational, biochemical, and biophysical methods. We also show that these inhibitors reduce L1 retrotransposition, L1-induced DNA damage, and inflammation reinforced by L1 in senescent cells. These inhibitors could be used for further pharmacological development and as tools to better understand the life cycle of this element and its impact on disease processes.

Indexed as

EndonucleasesLong Interspersed Nucleotide ElementsCellular SenescenceDeoxyribonuclease IDNA DamageEnzyme InhibitorsHumansSmall Molecule LibrariesDeoxyribonuclease IEndonucleasesEnzyme InhibitorsLINE-1 endonuclease, humanSmall Molecule Libraries

Identifiers

PMID38719805
PMCPMC11078990

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.