Evidence map›Paper›PMID 26411679›Full record

ArticleCell reports2015

Rad53-Mediated Regulation of Rrm3 and Pif1 DNA Helicases Contributes to Prevention of Aberrant Fork Transitions under Replication Stress.

Silvia Emma Rossi, Arta Ajazi, Walter Carotenuto, Marco Foiani, Michele Giannattasio

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
3.6field-weighted citation impact, top 6% 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

45 citing papers in PubMed, 61 citations in OpenAlex.

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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

5 authors at 1 institution in 1 country.

Silvia Emma RossiIFOM (Fondazione Istituto FIRC di Oncologia Molecolare), Via Adamello 16, 20139 Milan, Italy; Dipartimento di Bioscienze, Università degli Studi di Milano, Via Celoria 26, 20133 Milan, Italy.
Arta AjaziIFOM (Fondazione Istituto FIRC di Oncologia Molecolare), Via Adamello 16, 20139 Milan, Italy; Dipartimento di Bioscienze, Università degli Studi di Milano, Via Celoria 26, 20133 Milan, Italy.
Walter CarotenutoIFOM (Fondazione Istituto FIRC di Oncologia Molecolare), Via Adamello 16, 20139 Milan, Italy.
Marco FoianiIFOM (Fondazione Istituto FIRC di Oncologia Molecolare), Via Adamello 16, 20139 Milan, Italy; Dipartimento di Bioscienze, Università degli Studi di Milano, Via Celoria 26, 20133 Milan, Italy. Electronic address: marco.foiani@ifom.eu.
Michele GiannattasioIFOM (Fondazione Istituto FIRC di Oncologia Molecolare), Via Adamello 16, 20139 Milan, Italy; Dipartimento di Bioscienze, Università degli Studi di Milano, Via Celoria 26, 20133 Milan, Italy. Electronic address: michele.giannattasio@ifom.eu.
FIRC Institute of Molecular Oncology · IT

Funding

Telethon GGP12171
6 · The paper itself

Abstract

Replication stress activates the Mec1(ATR) and Rad53 kinases. Rad53 phosphorylates nuclear pores to counteract gene gating, thus preventing aberrant transitions at forks approaching transcribed genes. Here, we show that Rrm3 and Pif1, DNA helicases assisting fork progression across pausing sites, are detrimental in rad53 mutants experiencing replication stress. Rrm3 and Pif1 ablations rescue cell lethality, chromosome fragmentation, replisome-fork dissociation, fork reversal, and processing in rad53 cells. Through phosphorylation, Rad53 regulates Rrm3 and Pif1; phospho-mimicking rrm3 mutants ameliorate rad53 phenotypes following replication stress without affecting replication across pausing elements under normal conditions. Hence, the Mec1-Rad53 axis protects fork stability by regulating nuclear pores and DNA helicases. We propose that following replication stress, forks stall in an asymmetric conformation by inhibiting Rrm3 and Pif1, thus impeding lagging strand extension and preventing fork reversal; conversely, under unperturbed conditions, the peculiar conformation of forks encountering pausing sites would depend on active Rrm3 and Pif1.

Indexed as

Gene Expression Regulation, FungalBase SequenceBinding SitesCell Cycle ProteinsCheckpoint Kinase 2DNA, FungalDNA HelicasesDNA ReplicationIntracellular Signaling Peptides and ProteinsMolecular Sequence DataNuclear PorePhosphorylationProtein BindingProtein Serine-Threonine KinasesSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsCell Cycle ProteinsCheckpoint Kinase 2DNA, FungalDNA HelicasesIntracellular Signaling Peptides and ProteinsMEC1 protein, S cerevisiaePIF1 protein, S cerevisiaeProtein Serine-Threonine KinasesRAD53 protein, S cerevisiaeRrm3 protein, S cerevisiaeSaccharomyces cerevisiae Proteins

Identifiers

PMID26411679
PMCPMC4597105
OpenAlexW2098609152

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.