Evidence map›Paper›PMID 28916831›Full record

ArticleScientific reports2017

The melanocortin signaling cAMP axis accelerates repair and reduces mutagenesis of platinum-induced DNA damage.

Stuart G Jarrett, Katharine M Carter, Brent J Shelton, John A D'Orazio

RetractedOpen access · goldAbstract readRetracted Publication
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.4field-weighted citation impact, top 20% 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

10 citing papers in PubMed, 13 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Stuart G JarrettThe Markey Cancer Center, University of Kentucky College of Medicine, Lexington, Kentucky, 40536, USA.
Katharine M CarterThe Markey Cancer Center, University of Kentucky College of Medicine, Lexington, Kentucky, 40536, USA.
Brent J SheltonThe Markey Cancer Center, University of Kentucky College of Medicine, Lexington, Kentucky, 40536, USA.
John A D'OrazioThe Markey Cancer Center, University of Kentucky College of Medicine, Lexington, Kentucky, 40536, USA. jdorazio@uky.edu.ORCID http://orcid.org/0000-0003-1008-6234
University of Kentucky · US

Funding

University of Kentucky Markey Cancer Center Support Grant ECIA SupplementP30CA177558 · NCI · UNIVERSITY OF KENTUCKY · PI KATHLEEN L. O'CONNOR · 2013 to 2026
$38.3M
The role of Mc1r in melanocytic UV-induced DNA damage and repair responsesR01CA131075 · NCI · UNIVERSITY OF KENTUCKY · PI D'ORAZIO, JOHN A · 2010 to 2020
$3.3M
NCI NIH HHS P30 CA177558NCI NIH HHS R01 CA131075
6 · The paper itself

Abstract

Using primary melanocytes and HEK293 cells, we found that cAMP signaling accelerates repair of bi- and mono-functional platinum-induced DNA damage. Elevating cAMP signaling either by the agonistic MC1R ligand melanocyte stimulating hormone (MSH) or by pharmacologic cAMP induction by forskolin enhanced clearance of intrastrand cisplatin-adducts in melanocytes or MC1R-transfected HEK293 cells. MC1R antagonists human beta-defensin 3 and agouti signaling protein blocked MSH- but not forskolin-mediated enhancement of platinum-induced DNA damage. cAMP-enhanced repair of cisplatin-induced DNA damage was dependent on PKA-mediated phosphorylation of ATR on S435 which promoted ATR's interaction with the key NER factor xeroderma pigmentosum A (XPA) and facilitated recruitment of an XPA-ATR-pS435 complex to sites of cisplatin DNA damage. Moreover, we developed an oligonucleotide retrieval immunoprecipitation (ORiP) assay using a novel platinated-DNA substrate to establish kinetics of ATR-pS435 and XPA's associations with cisplatin-damaged DNA. Expression of a non-phosphorylatable ATR-S435A construct or deletion of A kinase-anchoring protein 12 (AKAP12) impeded platinum adduct clearance and prevented cAMP-mediated enhancement of ATR and XPA's associations with cisplatin-damaged DNA, indicating that ATR phosphorylation at S435 is necessary for cAMP-enhanced repair of platinum-induced damage and protection against cisplatin-induced mutagenesis. These data implicate cAMP signaling as a critical regulator of genomic stability against platinum-induced mutagenesis.

Indexed as

Cell LineCells, CulturedCyclic AMPDNA DamageDNA RepairGenomic InstabilityHEK293 CellsHumansMelanocortinsMutagenesisPlatinum CompoundsSignal TransductionCyclic AMPMelanocortinsPlatinum Compounds

Identifiers

PMID28916831
PMCPMC5601928
OpenAlexW2755981740

What OpenQuestion holds

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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.