Evidence map›Paper›PMID 32544229›Full record

ArticleNucleic acids research2020

Disease-associated DNA2 nuclease-helicase protects cells from lethal chromosome under-replication.

Benoît Falquet, Gizem Ölmezer, Franz Enkner, Dominique Klein, Kiran Challa, Rowin Appanah, Susan M Gasser, Ulrich Rass

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.0field-weighted citation impact, top 25% 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

13 citing papers in PubMed, 17 citations in OpenAlex.

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  9. International journal of molecular sciences · 2021
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  13. Lysine acetylation regulates the activity of nuclear Pif1.The Journal of biological chemistry · 2020
    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

8 authors at 3 institutions in 2 countries.

Benoît FalquetFriedrich Miescher Institute for Biomedical Research, CH-4058 Basel, Switzerland.
Gizem ÖlmezerFriedrich Miescher Institute for Biomedical Research, CH-4058 Basel, Switzerland.
Franz EnknerFriedrich Miescher Institute for Biomedical Research, CH-4058 Basel, Switzerland.
Dominique KleinFriedrich Miescher Institute for Biomedical Research, CH-4058 Basel, Switzerland.
Kiran ChallaFriedrich Miescher Institute for Biomedical Research, CH-4058 Basel, Switzerland.
Rowin AppanahGenome Damage and Stability Centre, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9RQ, UK.
Susan M GasserFriedrich Miescher Institute for Biomedical Research, CH-4058 Basel, Switzerland.
Ulrich RassFriedrich Miescher Institute for Biomedical Research, CH-4058 Basel, Switzerland.
Friedrich Miescher Institute · CHUniversity of Basel · CHUniversity of Sussex · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

DNA2 is an essential nuclease-helicase implicated in DNA repair, lagging-strand DNA synthesis, and the recovery of stalled DNA replication forks (RFs). In Saccharomyces cerevisiae, dna2Δ inviability is reversed by deletion of the conserved helicase PIF1 and/or DNA damage checkpoint-mediator RAD9. It has been suggested that Pif1 drives the formation of long 5'-flaps during Okazaki fragment maturation, and that the essential function of Dna2 is to remove these intermediates. In the absence of Dna2, 5'-flaps are thought to accumulate on the lagging strand, resulting in DNA damage-checkpoint arrest and cell death. In line with Dna2's role in RF recovery, we find that the loss of Dna2 results in severe chromosome under-replication downstream of endogenous and exogenous RF-stalling. Importantly, unfaithful chromosome replication in Dna2-mutant cells is exacerbated by Pif1, which triggers the DNA damage checkpoint along a pathway involving Pif1's ability to promote homologous recombination-coupled replication. We propose that Dna2 fulfils its essential function by promoting RF recovery, facilitating replication completion while suppressing excessive RF restart by recombination-dependent replication (RDR) and checkpoint activation. The critical nature of Dna2's role in controlling the fate of stalled RFs provides a framework to rationalize the involvement of DNA2 in Seckel syndrome and cancer.

Indexed as

DNA ReplicationCell Cycle CheckpointsCell Cycle ProteinsDNADNA DamageDNA HelicasesGenetic Diseases, InbornHumansMutationSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsCell Cycle ProteinsDNADNA2 protein, S cerevisiaeDNA HelicasesOkazaki fragmentsPIF1 protein, S cerevisiaerad9 proteinSaccharomyces cerevisiae Proteins

Identifiers

PMID32544229
PMCPMC7367196
OpenAlexW3035036511

What Socratic holds

Textmetadata
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 Socratic graph.