Evidence map›Paper›PMID 26443850›Full record

ArticleGenes & development2015

Local regulation of the Srs2 helicase by the SUMO-like domain protein Esc2 promotes recombination at sites of stalled replication.

Madhusoodanan Urulangodi, Marek Sebesta, Demis Menolfi, Barnabas Szakal, Julie Sollier, Alexandra Sisakova, Lumir Krejci, Dana Branzei

Open access · diamondAbstract read
In one paragraph

Article in Genes & development, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
–field-weighted citation impact
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

41 citing papers in PubMed, 57 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 2 countries.

Madhusoodanan UrulangodiFIRC (Fondazione Italiana per la Ricerca sul Cancro) Institute of Molecular Oncology (IFOM), 20139 Milan, Italy;
Marek SebestaFIRC (Fondazione Italiana per la Ricerca sul Cancro) Institute of Molecular Oncology (IFOM), 20139 Milan, Italy; National Centre for Biomolecular Research, Masaryk University, CZ-62500 Brno, Czech Republic;
Demis MenolfiFIRC (Fondazione Italiana per la Ricerca sul Cancro) Institute of Molecular Oncology (IFOM), 20139 Milan, Italy;
Barnabas SzakalFIRC (Fondazione Italiana per la Ricerca sul Cancro) Institute of Molecular Oncology (IFOM), 20139 Milan, Italy;
Julie SollierFIRC (Fondazione Italiana per la Ricerca sul Cancro) Institute of Molecular Oncology (IFOM), 20139 Milan, Italy;
Alexandra SisakovaDepartment of Biology, Masaryk University, CZ-62500 Brno, Czech Republic; International Clinical Research Center, Center for Biomolecular and Cellular Engineering, St. Anne's University Hospital Brno, CZ-656 91 Brno, Czech Republic.
Lumir KrejciNational Centre for Biomolecular Research, Masaryk University, CZ-62500 Brno, Czech Republic; Department of Biology, Masaryk University, CZ-62500 Brno, Czech Republic; International Clinical Research Center, Center for Biomolecular and Cellular Engineering, St. Anne's University Hospital Brno, CZ-656 91 Brno, Czech Republic.
Dana BranzeiFIRC (Fondazione Italiana per la Ricerca sul Cancro) Institute of Molecular Oncology (IFOM), 20139 Milan, Italy;
FIRC Institute of Molecular Oncology · ITSt. Anne's University Hospital Brno · CZMasaryk University · CZ

Funding

European Research Council 242928Telethon GGP12160
6 · The paper itself

Abstract

Accurate completion of replication relies on the ability of cells to activate error-free recombination-mediated DNA damage bypass at sites of perturbed replication. However, as anti-recombinase activities are also recruited to replication forks, how recombination-mediated damage bypass is enabled at replication stress sites remained puzzling. Here we uncovered that the conserved SUMO-like domain-containing Saccharomyces cerevisiae protein Esc2 facilitates recombination-mediated DNA damage tolerance by allowing optimal recruitment of the Rad51 recombinase specifically at sites of perturbed replication. Mechanistically, Esc2 binds stalled replication forks and counteracts the anti-recombinase Srs2 helicase via a two-faceted mechanism involving chromatin recruitment and turnover of Srs2. Importantly, point mutations in the SUMO-like domains of Esc2 that reduce its interaction with Srs2 cause suboptimal levels of Rad51 recruitment at damaged replication forks. In conclusion, our results reveal how recombination-mediated DNA damage tolerance is locally enabled at sites of replication stress and globally prevented at undamaged replicating chromosomes.

Indexed as

Cell Cycle ProteinsChromatinDNA DamageDNA HelicasesDNA ReplicationNuclear ProteinsPoint MutationProtein BindingRad51 RecombinaseRecombination, GeneticSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsCell Cycle ProteinsChromatinDNA HelicasesEsc2 protein, S cerevisiaeNuclear ProteinsRAD51 protein, S cerevisiaeRad51 RecombinaseSaccharomyces cerevisiae ProteinsSRS2 protein, S cerevisiaeDNA damage tolerancegenotoxic stressrecombinationreplicationSUMO

Identifiers

PMID26443850
PMCPMC4604347
OpenAlexW2198503610

What OpenQuestion holds

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LicenceCC BY
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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.