Evidence map›Paper›PMID 30239932›Full record

ArticleNucleic acids research2018

I260Q DNA polymerase β highlights precatalytic conformational rearrangements critical for fidelity.

Cary Liptak, Mariam M Mahmoud, Brian E Eckenroth, Marcus V Moreno, Kyle East, Khadijeh S Alnajjar, Ji Huang, Jamie B Towle-Weicksel, Sylvie Doublié, J Patrick Loria and 1 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
0.6field-weighted citation impact, top 31% 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

14 citing papers in PubMed, 16 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

11 authors at 2 institutions in 1 country.

Cary LiptakDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
Mariam M MahmoudDepartment of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Brian E EckenrothDepartment of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT 05405, USA.
Marcus V MorenoDepartment of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT 05405, USA.
Kyle EastDepartment of Chemistry, Yale University, New Haven, CT 06520, USA.
Khadijeh S AlnajjarDepartment of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Ji HuangDepartment of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Jamie B Towle-WeickselDepartment of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Sylvie DoubliéDepartment of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT 05405, USA.
J Patrick LoriaDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
Joann B SweasyDepartment of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Yale University · USUniversity of Vermont · US

Funding

PREDOCTORAL PROGRAM IN BIOPHYSICST32GM008283 · NIGMS · YALE UNIVERSITY · PI XIONG, YONG · 1988 to 2022
$10.5M
DNA POLYMERASE BETA AND MUTAGENESISR01CA080830 · NCI · YALE UNIVERSITY · PI SWEASY, JOANN B. · 1999 to 2018
$6.1M
Yale Cancer Biology Training GrantT32CA193200 · NCI · YALE UNIVERSITY · PI PETER M GLAZER, Qin Yan · 2016 to 2026
$3.6M
Structural Investigations Critical to Understanding DNA Damage Recognition and Repair in CancerR50CA233185 · NCI · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI Brian E. Eckenroth · 2018 to 2026
$1.2M
NMR dynamical characterization of WT and cancer-associated DNA polymeraseR01GM099990 · NIGMS · YALE UNIVERSITY · PI LORIA, JOSEPH P · 2012 to 2015
$1.2M
Perturbed Motions of DNAPolymeraseBeta Cancer Mutants Measured by NMRF31GM115223 · NIGMS · YALE UNIVERSITY · PI EAST, KYLE · 2015 to 2017
$119k
NCI NIH HHS R01 CA080830NCI NIH HHS R50 CA233185NCI NIH HHS T32 CA193200NIGMS NIH HHS F31 GM115223NIGMS NIH HHS R01 GM099990NIGMS NIH HHS T32 GM008283
6 · The paper itself

Abstract

DNA polymerase β (pol β) fills single nucleotide gaps in DNA during base excision repair and non-homologous end-joining. Pol β must select the correct nucleotide from among a pool of four nucleotides with similar structures and properties in order to maintain genomic stability during DNA repair. Here, we use a combination of X-ray crystallography, fluorescence resonance energy transfer and nuclear magnetic resonance to show that pol β's ability to access the appropriate conformations both before and upon binding to nucleotide substrates is integral to its fidelity. Importantly, we also demonstrate that the inability of the I260Q mutator variant of pol β to properly navigate this conformational landscape results in error-prone DNA synthesis. Our work reveals that precatalytic conformational rearrangements themselves are an important underlying mechanism of substrate selection by DNA pol β.

Indexed as

Codon, NonsenseNucleic Acid ConformationAmino Acid SubstitutionCatalysisCrystallography, X-RayDNADNA Polymerase betaDNA RepairDNA ReplicationFluorescence Resonance Energy TransferGenomic InstabilityGlutamic AcidIsoenzymesIsoleucineModels, MolecularNucleotidesCodon, NonsenseDNADNA Polymerase betaGlutamic AcidIsoenzymesIsoleucineNucleotides

Identifiers

PMID30239932
PMCPMC6237750
OpenAlexW2890323439

What OpenQuestion 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 OpenQuestion graph.