Evidence map›Paper›PMID 25601385›Full record

ArticleScientific reports2015

Checkpoint-dependent RNR induction promotes fork restart after replicative stress.

Esther C Morafraile, John F X Diffley, José Antonio Tercero, Mónica Segurado

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.2field-weighted citation impact, top 21% 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

15 citing papers in PubMed, 19 citations in OpenAlex.

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  12. Progerin sequestration of PCNA promotes replication fork collapse and mislocalization of XPA in laminopathy-related progeroid syndromes.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 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

4 authors at 3 institutions in 2 countries.

Esther C MorafraileInstituto de Biología Funcional y Genómica and Departamento de Microbiología y Genética, (CSIC/USAL), Campus Miguel de Unamuno, Salamanca 37007, Spain.
John F X DiffleyCancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, Herts. EN6 3LD, United Kingdom.
José Antonio TerceroCentro de Biología Molecular Severo Ochoa (CSIC/UAM), Cantoblanco, 28049 Madrid, Spain.
Mónica Segurado1] Instituto de Biología Funcional y Genómica and Departamento de Microbiología y Genética, (CSIC/USAL), Campus Miguel de Unamuno, Salamanca 37007, Spain [2] Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, Herts. EN6 3LD, United Kingdom [3] Centro de Biología Molecular Severo Ochoa (CSIC/UAM), Cantoblanco, 28049 Madrid, Spain.
Cancer Research UK · GBInstituto de Biología Funcional y Genómica · ESUniversidad Autónoma de Madrid · ES

Funding

Cancer Research UK 15669Worldwide Cancer Research 10-0270
6 · The paper itself

Abstract

The checkpoint kinase Rad53 is crucial to regulate DNA replication in the presence of replicative stress. Under conditions that interfere with the progression of replication forks, Rad53 prevents Exo1-dependent fork degradation. However, although EXO1 deletion avoids fork degradation in rad53 mutants, it does not suppress their sensitivity to the ribonucleotide reductase (RNR) inhibitor hydroxyurea (HU). In this case, the inability to restart stalled forks is likely to account for the lethality of rad53 mutant cells after replication blocks. Here we show that Rad53 regulates replication restart through the checkpoint-dependent transcriptional response, and more specifically, through RNR induction. Thus, in addition to preventing fork degradation, Rad53 prevents cell death in the presence of HU by regulating RNR-expression and localization. When RNR is induced in the absence of Exo1 and RNR negative regulators, cell viability of rad53 mutants treated with HU is increased and the ability of replication forks to restart after replicative stress is restored.

Indexed as

Cell Cycle ProteinsCell SurvivalCheckpoint Kinase 2DNA RepairDNA ReplicationExodeoxyribonucleasesGene Expression Regulation, FungalHydroxyureaMutationRibonucleotide ReductasesSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsCell Cycle ProteinsCheckpoint Kinase 2exodeoxyribonuclease IExodeoxyribonucleasesHydroxyureaRAD53 protein, S cerevisiaeRibonucleotide ReductasesSaccharomyces cerevisiae Proteins

Identifiers

PMID25601385
PMCPMC4298733
OpenAlexW2043112658

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.