ArticlePloS one2012
Pivotal role of inosine triphosphate pyrophosphatase in maintaining genome stability and the prevention of apoptosis in human cells.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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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.
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.
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Who cites it
25 citing papers in PubMed, 41 citations in OpenAlex.
- The CRISPR-associated adenosine deaminase Cad1 converts ATP to ITP to provide antiviral immunity.Cell · 2024Article
- Mixed infection of ITPase-encoding potyvirid and secovirid in Mercurialis perennis: evidences for a convergent euphorbia-specific viral counterstrike.Virology journal · 2024Article
- Changes inFrontiers in plant science · 2023Article
- Review
- Viral inosine triphosphatase: A mysterious enzyme with typical activity, but an atypical function.Molecular plant pathology · 2021Review
- Genetic screens in isogenic mammalian cell lines without single cell cloning.Nature communications · 2020Article
- Comment on "A commensal strain ofScience advances · 2019Article
- Molecular mechanism of substrate recognition and specificity of tRNARNA (New York, N.Y.) · 2018Article
- Review
- A commensal strain ofScience advances · 2018Article
- Gene dosage effects in yeast support broader roles for the LOG1, HAM1 and DUT1 genes in detoxification of nucleotide analogues.PloS one · 2018Article
- Measuring deaminated nucleotide surveillance enzyme ITPA activity with an ATP-releasing nucleotide chimera.Nucleic acids research · 2017Article
- Variant Inosine Triphosphatase Phenotypes Are Associated With Increased Ribavirin Triphosphate Levels.Journal of clinical pharmacology · 2017Article
- Article
- DCTPP1 attenuates the sensitivity of human gastric cancer cells to 5-fluorouracil by up-regulating MDR1 expression epigenetically.Oncotarget · 2016Article
- Identification of ITPA on chromosome 20 as a susceptibility gene for young-onset tuberculosis.Human genome variation · 2016Article
- The pivotal role of the mitochondrial amidoxime reducing component 2 in protecting human cells against apoptotic effects of the base analog N6-hydroxylaminopurine.The Journal of biological chemistry · 2015Article
- Article
- The human ITPA polymorphic variant P32T is destabilized by the unpacking of the hydrophobic core.Journal of structural biology · 2013Article
- Inosine triphosphate pyrophosphohydrolase (ITPA) polymorphic sequence variants in adult hematological malignancy patients and possible association with mitochondrial DNA defects.Journal of hematology & oncology · 2013Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Pure nucleotide precursor pools are a prerequisite for high-fidelity DNA replication and the suppression of mutagenesis and carcinogenesis. ITPases are nucleoside triphosphate pyrophosphatases that clean the precursor pools of the non-canonical triphosphates of inosine and xanthine. The precise role of the human ITPase, encoded by the ITPA gene, is not clearly defined. ITPA is clinically important because a widespread polymorphism, 94C>A, leads to null ITPase activity in erythrocytes and is associated with an adverse reaction to thiopurine drugs. We studied the cellular function of ITPA in HeLa cells using the purine analog 6-N hydroxylaminopurine (HAP), whose triphosphate is also a substrate for ITPA. In this study, we demonstrate that ITPA knockdown sensitizes HeLa cells to HAP-induced DNA breaks and apoptosis. The HAP-induced DNA damage and cytotoxicity observed in ITPA knockdown cells are rescued by an overexpression of the yeast ITPase encoded by the HAM1 gene. We further show that ITPA knockdown results in elevated mutagenesis in response to HAP treatment. Our studies reveal the significance of ITPA in preventing base analog-induced apoptosis, DNA damage and mutagenesis in human cells. This implies that individuals with defective ITPase are predisposed to genome damage by impurities in nucleotide pools, which is drastically augmented by therapy with purine analogs. They are also at an elevated risk for degenerative diseases and cancer.
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Registered trials
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.