Evidence map›Paper›PMID 25249630›Full record

ArticleNucleic acids research2014

Replication stress by Py-Im polyamides induces a non-canonical ATR-dependent checkpoint response.

Thomas F Martínez, John W Phillips, Kenneth K Karanja, Piotr Polaczek, Chieh-Mei Wang, Benjamin C Li, Judith L Campbell, Peter B Dervan

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.4field-weighted citation impact, top 18% 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

16 citing papers in PubMed, 27 citations in OpenAlex.

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  10. [Recognition study of double strand DNA with hairpin oligopolyamide].Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi · 2017
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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

8 authors at 1 institution in 1 country.

Thomas F MartínezDivision of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
John W PhillipsDivision of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Kenneth K KaranjaBraun Laboratories, California Institute of Technology, Pasadena, CA 91125, USA.
Piotr PolaczekBraun Laboratories, California Institute of Technology, Pasadena, CA 91125, USA.
Chieh-Mei WangDivision of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Benjamin C LiDivision of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Judith L CampbellBraun Laboratories, California Institute of Technology, Pasadena, CA 91125, USA.
Peter B DervanDivision of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA dervan@caltech.edu.
California Institute of Technology · US

Funding

SITE SPECIFIC CHEMICAL METHODS FOR CLEAVING GENOMIC DNAR01GM051747 · NIGMS · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI DERVAN, PETER B · 1995 to 2014
$6.2M
SEQUENCE SPECIFIC RECOGNITION OF DOUBLE HELICAL DNAR01GM027681 · NIGMS · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI DERVAN, PETER B · 1985 to 2017
$4.5M
Enzyme Interactions at the DNA Replication ForkR01GM078666 · NIGMS · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI CAMPBELL, JUDITH L · 2006 to 2009
$1.5M
Interrogation of Androgen Receptor:Forkhead Interaction Using Py-Im PolyamidesF31CA159896 · NCI · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI MARTINEZ, THOMAS FARID · 2011 to 2014
$165k
NCI NIH HHS F31 CA159896NCI NIH HHS F31CA159896NIGMS NIH HHS R01 GM027681NIGMS NIH HHS R01 GM051747NIGMS NIH HHS R01GM07866NIGMS NIH HHS R01 GM078666NIGMS NIH HHS R01GM27681NIGMS NIH HHS R01GM51747
6 · The paper itself

Abstract

Pyrrole-imidazole polyamides targeted to the androgen response element were cytotoxic in multiple cell lines, independent of intact androgen receptor signaling. Polyamide treatment induced accumulation of S-phase cells and of PCNA replication/repair foci. Activation of a cell cycle checkpoint response was evidenced by autophosphorylation of ATR, the S-phase checkpoint kinase, and by recruitment of ATR and the ATR activators RPA, 9-1-1, and Rad17 to chromatin. Surprisingly, ATR activation was accompanied by only a slight increase in single-stranded DNA, and the ATR targets RPA2 and Chk1, a cell cycle checkpoint kinase, were not phosphorylated. However, ATR activation resulted in phosphorylation of the replicative helicase subunit MCM2, an ATR effector. Polyamide treatment also induced accumulation of monoubiquitinated FANCD2, which is recruited to stalled replication forks and interacts transiently with phospho-MCM2. This suggests that polyamides induce replication stress that ATR can counteract independently of Chk1 and that the FA/BRCA pathway may also be involved in the response to polyamides. In biochemical assays, polyamides inhibit DNA helicases, providing a plausible mechanism for S-phase inhibition.

Indexed as

Stress, PhysiologicalAtaxia Telangiectasia Mutated ProteinsCell LineCheckpoint Kinase 2DNA BreaksDNA HelicasesDNA RepairDNA ReplicationFanconi Anemia Complementation Group D2 ProteinHumansImidazolesMinichromosome Maintenance Complex Component 2NylonsProliferating Cell Nuclear AntigenPyrrolesReplication Protein AAtaxia Telangiectasia Mutated ProteinsATR protein, humanCheckpoint Kinase 2DNA HelicasesFanconi Anemia Complementation Group D2 ProteinImidazolesMinichromosome Maintenance Complex Component 2NylonsProliferating Cell Nuclear AntigenPyrrolesReplication Protein A

Identifiers

PMID25249630
PMCPMC4191428
OpenAlexW2164443538

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.