Evidence map›Paper›PMID 31287140›Full record

ArticleNucleic acids research2019

Stability and sub-cellular localization of DNA polymerase β is regulated by interactions with NQO1 and XRCC1 in response to oxidative stress.

Qingming Fang, Joel Andrews, Nidhi Sharma, Anna Wilk, Jennifer Clark, Jana Slyskova, Christopher A Koczor, Hannes Lans, Aishwarya Prakash, Robert W Sobol

Abstract read
In one paragraph

Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing 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

21 citing papers in PubMed.

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  8. Molecular editing ofRSC medicinal chemistry · 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

10 authors.

Qingming FangUniversity of South Alabama Mitchell Cancer Institute, 1660 Springhill Avenue, Mobile, AL 36604, USA.
Joel AndrewsUniversity of South Alabama Mitchell Cancer Institute, 1660 Springhill Avenue, Mobile, AL 36604, USA.
Nidhi SharmaUniversity of South Alabama Mitchell Cancer Institute, 1660 Springhill Avenue, Mobile, AL 36604, USA.
Anna WilkUniversity of South Alabama Mitchell Cancer Institute, 1660 Springhill Avenue, Mobile, AL 36604, USA.
Jennifer ClarkUniversity of South Alabama Mitchell Cancer Institute, 1660 Springhill Avenue, Mobile, AL 36604, USA.
Jana SlyskovaDepartment of Molecular Genetics, Erasmus MC, Erasmus University Medical Center Rotterdam, 3000 CA Rotterdam, The Netherlands.
Christopher A KoczorUniversity of South Alabama Mitchell Cancer Institute, 1660 Springhill Avenue, Mobile, AL 36604, USA.
Hannes LansDepartment of Molecular Genetics, Erasmus MC, Erasmus University Medical Center Rotterdam, 3000 CA Rotterdam, The Netherlands.
Aishwarya PrakashUniversity of South Alabama Mitchell Cancer Institute, 1660 Springhill Avenue, Mobile, AL 36604, USA.
Robert W SobolUniversity of South Alabama Mitchell Cancer Institute, 1660 Springhill Avenue, Mobile, AL 36604, USA.

Funding

A Systems Approach to Mapping the DNA Damage ResponseR01ES014811 · NIEHS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI IDEKER, TREY · 2005 to 2021
$8.6M
Novel approaches to enhance tumor cell cytotoxicity of alkylating agentsR01CA148629 · NCI · UNIVERSITY OF SOUTH ALABAMA · PI SOBOL, ROBERT W · 2010 to 2021
$3.4M
Repair of Environmentally and Endogenously Induced Mitochondrial-DNA DamageR00ES024417 · NIEHS · UNIVERSITY OF SOUTH ALABAMA · PI PRAKASH, AISHWARYA · 2016 to 2018
$747k
NCI NIH HHS R01 CA148629NIEHS NIH HHS R00 ES024417NIEHS NIH HHS R01 ES014811
6 · The paper itself

Abstract

Protein-protein interactions regulate many essential enzymatic processes in the cell. Somatic mutations outside of an enzyme active site can therefore impact cellular function by disruption of critical protein-protein interactions. In our investigation of the cellular impact of the T304I cancer mutation of DNA Polymerase β (Polβ), we find that mutation of this surface threonine residue impacts critical Polβ protein-protein interactions. We show that proteasome-mediated degradation of Polβ is regulated by both ubiquitin-dependent and ubiquitin-independent processes via unique protein-protein interactions. The ubiquitin-independent proteasome pathway regulates the stability of Polβ in the cytosol via interaction between Polβ and NAD(P)H quinone dehydrogenase 1 (NQO1) in an NADH-dependent manner. Conversely, the interaction of Polβ with the scaffold protein X-ray repair cross complementing 1 (XRCC1) plays a role in the localization of Polβ to the nuclear compartment and regulates the stability of Polβ via a ubiquitin-dependent pathway. Further, we find that oxidative stress promotes the dissociation of the Polβ/NQO1 complex, enhancing the interaction of Polβ with XRCC1. Our results reveal that somatic mutations such as T304I in Polβ impact critical protein-protein interactions, altering the stability and sub-cellular localization of Polβ and providing mechanistic insight into how key protein-protein interactions regulate cellular responses to stress.

Indexed as

Oxidative StressCell Line, TumorChromatinColonic NeoplasmsDNA Polymerase betaEnzyme StabilityHumansMutationNADNAD(P)H Dehydrogenase (Quinone)Proteasome Endopeptidase ComplexUbiquitinationX-ray Repair Cross Complementing Protein 1ChromatinDNA Polymerase betaNADNAD(P)H Dehydrogenase (Quinone)NQO1 protein, humanPOLB protein, humanProteasome Endopeptidase ComplexX-ray Repair Cross Complementing Protein 1XRCC1 protein, human

Identifiers

PMID31287140
PMCPMC6614843

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Registered trials

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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.