Evidence map›Paper›PMID 32299912›Full record

ArticleThe Journal of biological chemistry2020

Genome-wide single-nucleotide resolution of oxaliplatin-DNA adduct repair in drug-sensitive and -resistant colorectal cancer cell lines.

Courtney M Vaughn, Christopher P Selby, Yanyan Yang, David S Hsu, Aziz Sancar

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
1.5field-weighted citation impact, top 15% 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

21 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Multi-Pathway Study for Oxaliplatin Resistance Reduction.Current issues in molecular biology · 2025
    Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Prostaglandin FWorld journal of gastroenterology · 2023
    Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Review
  18. LncRNA LIMp27 Regulates the DNA Damage Response through p27 in p53-Defective Cancer Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023
    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

5 authors at 2 institutions in 1 country.

Courtney M VaughnDepartment of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599-7260.ORCID 0000-0002-2564-0181
Christopher P SelbyDepartment of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599-7260.
Yanyan YangDepartment of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599-7260.
David S HsuDuke University Medical Center, Durham, North Carolina 27710.
Aziz SancarDepartment of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599-7260 aziz_sancar@med.unc.edu.ORCID 0000-0001-6469-4900
University of North Carolina at Chapel Hill · USDuke Medical Center · US

Funding

UNC-CH CENTER FOR ENVIRONMENTAL HEALTH &SUSCEPTIBILITYP30ES010126 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Stephanie Engel · 2001 to 2026
$36.3M
Molecular Mechanism of Mammalian DNA Excision Repair, DNA Damage Checkpoints and the Circadian ClockR35GM118102 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI AZIZ SANCAR · 2016 to 2026
$10.6M
NRSA IN GENETICST32GM007092 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SEKELSKY, JEFF J. · 1985 to 2019
$5.9M
Single Nucleotide Resolution Map of Formation and Repair of Bulky Adducts in the Human GenomeR01ES027255 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SANCAR, AZIZ · 2016 to 2020
$2.3M
Genome-wide Patterns of DNA Damage and Repair in Resistance to Platinum-Based ChemotherapyF30CA225060 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI VAUGHN, COURTNEY MICHELLE · 2019 to 2021
$115k
NCI NIH HHS F30 CA225060NIEHS NIH HHS P30 ES010126NIEHS NIH HHS R01 ES027255NIGMS NIH HHS R35 GM118102NIGMS NIH HHS T32 GM007092
6 · The paper itself

Abstract

Platinum-based chemotherapies, including oxaliplatin, are a mainstay in the management of solid tumors and induce cell death by forming intrastrand dinucleotide DNA adducts. Despite their common use, they are highly toxic, and approximately half of cancer patients have tumors that are either intrinsically resistant or develop resistance. Previous studies suggest that this resistance is mediated by variations in DNA repair levels or net drug influx. Here, we aimed to better define the roles of nucleotide excision repair and DNA damage in platinum chemotherapy resistance by profiling DNA damage and repair efficiency in seven oxaliplatin-sensitive and three oxaliplatin-resistant colorectal cancer cell lines. We assayed DNA repair indirectly as toxicity and directly measured bulky adduct formation and removal from the genome by slot blot and repair capacity in an excision assay, and used excision repair sequencing (XR-seq) to map repair events genome-wide at single-nucleotide resolution. Using this combinatorial approach and proxies for oxaliplatin-DNA damage, we observed no significant differences in repair efficiency that could explain the relative sensitivities and chemotherapy resistances of these cell lines. In contrast, the levels of oxaliplatin-induced DNA damage were significantly lower in the resistant cells, indicating that decreased damage formation, rather than increased damage repair, is a major determinant of oxaliplatin resistance in these cell lines. XR-seq-based analysis of gene expression revealed up-regulation of membrane transport pathways in the resistant cells, and these pathways may contribute to resistance. In conclusion, additional research is needed to characterize the factors mitigating cellular DNA damage formation by platinum compounds.

Indexed as

DNA DamageDNA RepairDrug Resistance, NeoplasmColorectal NeoplasmsDNA AdductsDNA, NeoplasmHCT116 CellsHumansOxaliplatinDNA AdductsDNA, NeoplasmOxaliplatinchemoresistancechemotherapycolorectal cancercytotoxicityDNA damageDNA repairdrug resistanceexcision repair sequencing (XR-seq)genomicsnucleotide excision repairoxaliplatin resistance

Identifiers

PMID32299912
PMCPMC7261789
OpenAlexW3017114811

What OpenQuestion holds

Textmetadata
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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.