Evidence map›Paper›PMID 38194346›Full record

ArticleCell reports2024

Oxidative guanine base damage plays a dual role in regulating productive ALT-associated homology-directed repair.

Sanjana A Thosar, Ryan P Barnes, Ariana Detwiler, Ragini Bhargava, Anne Wondisford, Roderick J O'Sullivan, Patricia L Opresko

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
5.4field-weighted citation impact, top 4% 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

19 citing papers in PubMed, 23 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Review
  9. Article
  10. Review
  11. Article
  12. Oxidative Stress and DNA Damage at Telomeres.Cold Spring Harbor perspectives in biology · 2025
    Review
  13. Article
  14. Review
  15. Review
  16. Article
  17. Article
  18. Review
  19. 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

7 authors at 1 institution in 1 country.

Sanjana A ThosarDepartment of Environmental and Occupational Health, University of Pittsburgh School of Public Health, Pittsburgh, PA, USA; UPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Ryan P BarnesDepartment of Environmental and Occupational Health, University of Pittsburgh School of Public Health, Pittsburgh, PA, USA; UPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Ariana DetwilerDepartment of Environmental and Occupational Health, University of Pittsburgh School of Public Health, Pittsburgh, PA, USA; UPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Ragini BhargavaUPMC Hillman Cancer Center, Pittsburgh, PA, USA; Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Anne WondisfordUPMC Hillman Cancer Center, Pittsburgh, PA, USA; Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Roderick J O'SullivanUPMC Hillman Cancer Center, Pittsburgh, PA, USA; Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Patricia L OpreskoDepartment of Environmental and Occupational Health, University of Pittsburgh School of Public Health, Pittsburgh, PA, USA; UPMC Hillman Cancer Center, Pittsburgh, PA, USA; Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address: plo4@pitt.edu.
University of Pittsburgh · US

Funding

VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHRISTOPHER J. BAKKENIST · 1988 to 2026
$158.0M
Supplement to Promote DiversityR35ES030396 · NIEHS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Patricia L Opresko · 2019 to 2026
$7.5M
Roles of Telomeric Oxidative DNA Lesions in Telomere Length RegulationR01CA207342 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Sua Myong, Patricia L Opresko · 2017 to 2026
$3.7M
Inhibition of the ALT pathway by interfering with Poly-ADP-Ribose metabolismR01CA207209 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Roderick O'Sullivan · 2016 to 2026
$3.6M
Co-Regulation of Alternative Lengthening of Telomeres and Chromatin Dynamics in ATRX-DAXX deficient cancer cellsR01CA262316 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Roderick O'Sullivan · 2022 to 2026
$2.2M
Predoctoral Training in Pharmacological Sciences (Resubmission)T32GM133332 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Tija C. Jacob, Francisco Jose Schopfer · 2020 to 2026
$1.8M
Investigating the Cellular Impact of 8-oxo-Guanine on DNA Replication and Genome StabilityR00ES033771 · NIEHS · UNIVERSITY OF KANSAS MEDICAL CENTER · PI Ryan P Barnes · 2024 to 2026
$747k
Investigating the Cellular Impact of 8-oxo-Guanine on DNA Replication and Genome StabilityK99ES033771 · NIEHS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BARNES, RYAN P · 2022 to 2023
$214k
Understanding the impact of DNA ADP-ribosylation on telomere function in cancer cellsF30CA278287 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI WONDISFORD, ANNE · 2023 to 2025
$107k
Investigating the Impact of Telomere Specific Oxidative Base Damage in Cellular AgingF32AG067710 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BARNES, RYAN P · 2020 to 2021
$106k
NCI NIH HHS F30 CA278287NCI NIH HHS P30 CA047904NCI NIH HHS R01 CA207209NCI NIH HHS R01 CA207342NCI NIH HHS R01 CA262316NIA NIH HHS F32 AG067710NIEHS NIH HHS K99 ES033771NIEHS NIH HHS R00 ES033771NIEHS NIH HHS R35 ES030396NIGMS NIH HHS T32 GM133332
6 · The paper itself

Abstract

Cancer cells maintain telomeres by upregulating telomerase or alternative lengthening of telomeres (ALT) via homology-directed repair at telomeric DNA breaks. 8-Oxoguanine (8oxoG) is a highly prevalent endogenous DNA lesion in telomeric sequences, altering telomere structure and telomerase activity, but its impact on ALT is unclear. Here, we demonstrate that targeted 8oxoG formation at telomeres stimulates ALT activity and homologous recombination specifically in ALT cancer cells. Mechanistically, an acute 8oxoG induction increases replication stress, as evidenced by increased telomere fragility and ATR kinase activation at ALT telomeres. Furthermore, ALT cells are more sensitive to chronic telomeric 8oxoG damage than telomerase-positive cancer cells, consistent with increased 8oxoG-induced replication stress. However, telomeric 8oxoG production in G2 phase, when ALT telomere elongation occurs, impairs telomeric DNA synthesis. Our study demonstrates that a common oxidative base lesion has a dual role in regulating ALT depending on when the damage arises in the cell cycle.

Indexed as

TelomeraseGuanineOxidative StressTelomereTelomere HomeostasisGuanineTelomerase8-oxoguaninealternative lengthening of telomerescancer cell proliferationCP: Molecular biologyhomology directed repairoxidative DNA damagereplication stresstelomere maitenance

Identifiers

PMID38194346
PMCPMC10851105
OpenAlexW4390787309

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.