Evidence map›Paper›PMID 25565400›Full record

ArticleCell cycle (Georgetown, Tex.)2015

Decarbamoyl mitomycin C (DMC) activates p53-independent ataxia telangiectasia and rad3 related protein (ATR) chromatin eviction.

Gu Xiao, Pao Kue, Rahul Bhosle, Jill Bargonetti

Open access · bronzeAbstract read
In one paragraph

Article in Cell cycle (Georgetown, Tex.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.8field-weighted citation impact, top 29% 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

11 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
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  8. Article
  9. Article
  10. DNA repair in ischemic acute kidney injury.American journal of physiology. Renal physiology · 2017
    Review
  11. 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

4 authors at 3 institutions in 1 country.

Gu Xiaoa Department of Biological Sciences; Hunter College and The Graduate Center Biology Program ; City University of New York ; New York , NY USA.
Pao Kue
Rahul Bhosle
Jill Bargonetti
City University of New York · USHunter College · USThe Graduate Center, CUNY · US

Funding

Basic and Translational Research Center for Reducing Health DisparitiesG12MD007599 · NIMHD · HUNTER COLLEGE · PI ANGULO, JESUS A · 2012 to 2017
$14.6M
p53-Independent Cell Death Signaling by Mitomycin DNA AdductsSC1CA137843 · NCI · HUNTER COLLEGE · PI BARGONETTI, JILL E. · 2008 to 2011
$1.3M
NCI NIH HHS 1SC1 CA137843
6 · The paper itself

Abstract

Interstrand crosslinks induce DNA replication fork stalling that in turn activates the ATR-dependent checkpoint and DNA repair on nuclear chromatin. Mitomycin C (MC) and Decarbamoyl Mitomycin C (DMC) induce different types of DNA crosslinks with DMC being a more cytotoxic agent. We previously reported that the novel DMC induced β-interstrand DNA crosslinks induce a p53-independent form of cell death. The p53-independent DMC cytotoxicity associates with the activation, and subsequent depletion, of Chk1. In this study we further dissect the novel DMC signal transduction pathway and asked how it influences chromatin-associated proteins. We found that treatment with DMC, but not MC, stimulated the disassociation of ATR from chromatin and re-localization of ATR to the cytoplasm. The chromatin eviction of ATR was coupled with the formation of nuclear Rad51 foci and the phosphorylation of Chk1. Furthermore, DMC but not MC, activated expression of gadd45α mRNA. Importantly, knocking down p53 via shRNA did not inhibit the DMC-induced disassociation of ATR from chromatin or reduce the activation of transcription of gadd45α. Our results suggest that DMC induces a p53-independent disassociation of ATR from chromatin that facilitates Chk1 checkpoint activation and Rad51 chromatin recruitment. Our findings provide evidence that ATR chromatin eviction in breast cancer cells is an area of study that should be focused on for inducing p53-independent cell death.

Indexed as

Ataxia Telangiectasia Mutated ProteinsCell Cycle ProteinsCell DeathCheckpoint Kinase 1ChromatinDNADNA DamageGADD45 ProteinsHomologous RecombinationHumansMCF-7 CellsMitomycinsModels, BiologicalNuclear Proteinsp38 Mitogen-Activated Protein KinasesPhosphorylation10-decarbamoylmitomycin CAtaxia Telangiectasia Mutated ProteinsATR protein, humanCell Cycle ProteinsCheckpoint Kinase 1CHEK1 protein, humanChromatinDNAGADD45A protein, humanGADD45 ProteinsMitomycinsNuclear Proteinsp38 Mitogen-Activated Protein KinasesPhosphoserineProtein KinasesRad51 RecombinaseTumor Suppressor Protein p53ATRATR, Ataxia Telangiectasia and Rad3 Relatedbreast cancerCdc25, cell division cycle 25.cell deathChIP, chromatin immunoprecipitationChk1, checkpoint serine/threonine protein kinase 1chromatinDDR, DNA damage responseDMC, Decarbamoyl Mitomycin CDOX, doxycyclineHR, homologous recombinationICLs, interstrand cross-linksinterstrand crosslinkMC, Mitomycin Cmitomycin CNER, nuclear excision repairp53PCNA, Proliferating Cell Nuclear AntigenRPA, replication protein ATNBCs, triple negative breast cancers

Identifiers

PMID25565400
PMCPMC4418290
OpenAlexW1500493173

What OpenQuestion holds

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LicenceCC BY-NC
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.