Evidence map›Paper›PMID 28180291›Full record

ArticleNucleic acids research2017

Yeast DNA polymerase ζ maintains consistent activity and mutagenicity across a wide range of physiological dNTP concentrations.

Olga V Kochenova, Rachel Bezalel-Buch, Phong Tran, Alena V Makarova, Andrei Chabes, Peter M J Burgers, Polina V Shcherbakova

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
0.9field-weighted citation impact, top 23% 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

19 citing papers in PubMed, 32 citations in OpenAlex.

  1. Article
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  6. eLife · 2024
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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

7 authors at 3 institutions in 2 countries.

Olga V KochenovaEppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA.
Rachel Bezalel-BuchDepartment of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, USA.
Phong TranDepartment of Medical Biochemistry and Biophysics and Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, Sweden.
Alena V MakarovaDepartment of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, USA.
Andrei ChabesDepartment of Medical Biochemistry and Biophysics and Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, Sweden.
Peter M J BurgersDepartment of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, USA.
Polina V ShcherbakovaEppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA.
Washington University in St. Louis · USUmeå University · SEUniversity of Nebraska Medical Center · US

Funding

MECHANISMS OF DNA REPLICATION AND MAINTENANCE IN EUKARYOTESR35GM118129 · NIGMS · WASHINGTON UNIVERSITY · PI BURGERS, PETER M · 2016 to 2025
$6.7M
ENZYMOLOGY OF REPLICATION OF YEAST CHROMOSOMAL DNAR01GM032431 · NIGMS · WASHINGTON UNIVERSITY · PI BURGERS, PETER M · 1985 to 2015
$6.5M
Translesion Synthesis DNA Polymerases and Genome InstabilityR01ES015869 · NIEHS · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI SHCHERBAKOVA, POLINA V · 2009 to 2023
$4.7M
NIEHS NIH HHS R01 ES015869NIGMS NIH HHS R01 GM032431NIGMS NIH HHS R35 GM118129
6 · The paper itself

Abstract

In yeast, dNTP pools expand drastically during DNA damage response. We show that similar dNTP elevation occurs in strains, in which intrinsic replisome defects promote the participation of error-prone DNA polymerase ζ (Polζ) in replication of undamaged DNA. To understand the significance of dNTP pools increase for Polζ function, we studied the activity and fidelity of four-subunit Polζ (Polζ4) and Polζ4-Rev1 (Polζ5) complexes in vitro at ‘normal S-phase’ and ‘damage-response’ dNTP concentrations. The presence of Rev1 inhibited the activity of Polζ and greatly increased the rate of all three ‘X-dCTP’ mispairs, which Polζ4 alone made extremely inefficiently. Both Polζ4 and Polζ5 were most promiscuous at G nucleotides and frequently generated multiple closely spaced sequence changes. Surprisingly, the shift from ‘S-phase’ to ‘damage-response’ dNTP levels only minimally affected the activity, fidelity and error specificity of Polζ complexes. Moreover, Polζ-dependent mutagenesis triggered by replisome defects or UV irradiation in vivo was not decreased when dNTP synthesis was suppressed by hydroxyurea, indicating that Polζ function does not require high dNTP levels. The results support a model wherein dNTP elevation is needed to facilitate non-mutagenic tolerance pathways, while Polζ synthesis represents a unique mechanism of rescuing stalled replication when dNTP supply is low.

Indexed as

DeoxyribonucleotidesDNA DamageDNA-Directed DNA PolymeraseDNA, FungalDNA ReplicationMutagenesisNucleotidyltransferasesProtein SubunitsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsY-Family DNA PolymerasesDeoxyribonucleotidesDNA-Directed DNA PolymeraseDNA, FungalDNA polymerase zetaNucleotidyltransferasesProtein SubunitsREV1 protein, S cerevisiaeSaccharomyces cerevisiae ProteinsY-Family DNA Polymerases

Identifiers

PMID28180291
PMCPMC5388397
OpenAlexW2559487434

What OpenQuestion holds

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LicenceCC BY-NC
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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.