Evidence map›Paper›PMID 28945288›Full record

ArticleEnvironmental and molecular mutagenesis2018

Thiopurine-induced mitotic catastrophe in Rad51d-deficient mammalian cells.

Michael D Wyatt, Nicole M Reilly, Shikha Patel, Preeti Rajesh, Gary P Schools, Phillip G Smiraldo, Douglas L Pittman

Open access · greenAbstract read
In one paragraph

Article in Environmental and molecular mutagenesis, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact, top 89% 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

0 citing papers in PubMed, 4 citations in OpenAlex.

No citing paper in PubMed yet.

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.

Michael D WyattDepartment of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, Columbia, South Carolina, 29208.ORCID 0000-0003-1815-9565
Nicole M ReillyDepartment of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, Columbia, South Carolina, 29208.
Shikha PatelDepartment of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, Columbia, South Carolina, 29208.
Preeti RajeshDepartment of Biotechnology, Sri Guru Granth Sahib World University, Fatehgarh Sahib, Punjab, 140406, India.
Gary P SchoolsDepartment of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, Columbia, South Carolina, 29208.
Phillip G SmiraldoNAMSA, Northwood, Ohio, 43619.
Douglas L PittmanDepartment of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, Columbia, South Carolina, 29208.
University of South Carolina · USNational Alliance on Mental Illness · USSri Guru Granth Sahib World University · IN

Funding

TISSUE BIOREPOSITORYP20RR017698 · NCRR · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI FAYAD, RAJA · 2002 to 2011
$22.5M
TISSUE BIOREPOSITORY COREP30GM103336 · NIGMS · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI BERGER, FRANKLIN G. · 2013 to 2017
$5.4M
Thymineless stress, DNA repair and recombinationR01CA100450 · NCI · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI WYATT, MICHAEL D. · 2004 to 2008
$1.3M
RAD51-dependent homologous recombination and thiopurine treatments for cancerR15CA223956 · NCI · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI WYATT, MICHAEL D. · 2018 to 2018
$433k
Ubiquitin-mediated regulation of the RAD51D homologous recombination proteinR15GM110615 · NIGMS · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI PITTMAN, DOUGLAS LEE · 2014 to 2014
$325k
NCI NIH HHS R01 CA100450NCI NIH HHS R15 CA223956NCRR NIH HHS P20 RR017698NIGMS NIH HHS P30 GM103336NIGMS NIH HHS R15 GM110615
6 · The paper itself

Abstract

Thiopurines are part of a clinical regimen used for the treatment of autoimmune disorders and childhood acute lymphoblastic leukemia. However, despite these successes, there are also unintended consequences such as therapy-induced cancer in long-term survivors. Therefore, a better understanding of cellular responses to thiopurines will lead to improved and personalized treatment strategies. RAD51D is an important component of homologous recombination (HR), and our previous work established that mammalian cells defective for RAD51D are more sensitive to the thiopurine 6-thioguanine (6TG) and have dramatically increased numbers of multinucleated cells and chromosome instability. 6TG is capable of being incorporated into telomeres, and interestingly, RAD51D contributes to telomere maintenance, although the precise function of RAD51D at the telomeres remains unclear. We sought here to investigate: (1) the activity of RAD51D at telomeres, (2) the contribution of RAD51D to protect against 6TG-induced telomere damage, and (3) the fates of Rad51d-deficient cells following 6TG treatment. These results demonstrate that RAD51D is required for maintaining the telomeric 3' overhangs. As measured by γ-H2AX induction and foci formation, 6TG induced DNA damage in Rad51d-proficient and Rad51d-deficient cells. However, the extent of γ-H2AX telomere localization following 6TG treatment was higher in Rad51d-deficient cells than in Rad51d-proficient cells. Using live-cell imaging of 6TG-treated Rad51d-deficient cells, two predominant forms of mitotic catastrophe were found to contribute to the formation of multinucleated cells, failed division and restitution. Collectively, these findings provide a unique window into the role of the RAD51D HR protein during thiopurine induction of mitotic catastrophe. Environ. Mol. Mutagen. 59:38-48, 2018. © 2017 Wiley Periodicals, Inc.

Indexed as

AnimalsCell LineChromosomal InstabilityDNA-Binding ProteinsDNA DamageHomologous RecombinationMiceMitosisTelomereThioguanineDNA-Binding ProteinsRad51d protein, mouseThioguanine6-thioguanineH2AXhomologous recombinationmitotic catastrophetelomeres

Identifiers

PMID28945288
PMCPMC5771848
OpenAlexW2759275632

What OpenQuestion holds

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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.