ArticleThe Journal of biological chemistry2013
Inositol pyrophosphate synthesis by inositol hexakisphosphate kinase 1 is required for homologous recombination repair.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 56 citations in OpenAlex.
- Inositol pyrophosphate kinases in health and disease.FEBS letters · 2026Review
- Novel and unusualJournal of clinical pathology · 2025Article
- (PP)-InsP Affinity Probes for Target Characterization by Immunoblotting and Mass Spectrometry.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Article
- SMAD4 Limits PARP1 dependent DNA Repair to Render Pancreatic Cancer Cells Sensitive to Radiotherapy.Cell death & disease · 2024Article
- Insights into the roles of inositol hexakisphosphate kinase 1 (IP6K1) in mammalian cellular processes.The Journal of biological chemistry · 2024Review
- Functions, Mechanisms, and therapeutic applications of the inositol pyrophosphates 5PP-InsPJournal of cardiovascular translational research · 2024Review
- Opi1-mediated transcriptional modulation orchestrates genotoxic stress response in budding yeast.Genetics · 2023Article
- Development of Novel IP6K Inhibitors for the Treatment of Obesity and Obesity-Induced Metabolic Dysfunctions.Journal of medicinal chemistry · 2022Article
- Inositol hexakisphosphate kinase-2 non-catalytically regulates mitophagy by attenuating PINK1 signaling.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Regulation of plant biotic interactions and abiotic stress responses by inositol polyphosphates.Frontiers in plant science · 2022Review
- Wheat inositol pyrophosphate kinase TaVIH2-3B modulates cell-wall composition and drought tolerance in Arabidopsis.BMC biology · 2021Article
- The Key Role of IPMolecules (Basel, Switzerland) · 2020Review
- Inositol Polyphosphate Multikinase (Genes · 2019Article
- The inositol pyrophosphate pathway in health and diseases.Biological reviews of the Cambridge Philosophical Society · 2018Review
- Nuclear phosphoinositide regulation of chromatin.Journal of cellular physiology · 2018Review
- The inositol pyrophosphate synthesis pathway in Trypanosoma brucei is linked to polyphosphate synthesis in acidocalcisomes.Molecular microbiology · 2017Article
- The significance of the 1-kinase/1-phosphatase activities of the PPIP5K family.Advances in biological regulation · 2017Review
- Development of a homogenous high-throughput assay for inositol hexakisphosphate kinase 1 activity.PloS one · 2017Article
- Inositol Pyrophosphates: Energetic, Omnipresent and Versatile Signalling Molecules.Journal of the Indian Institute of Science · 2017Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Inositol pyrophosphates, such as diphosphoinositol pentakisphosphate (IP(7)), are water-soluble inositol phosphates that contain high energy diphosphate moieties on the inositol ring. Inositol hexakisphosphate kinase 1 (IP6K1) participates in inositol pyrophosphate synthesis, converting inositol hexakisphosphate (IP(6)) to IP(7). In the present study, we show that mouse embryonic fibroblasts (MEFs) lacking IP6K1 exhibit impaired DNA damage repair via homologous recombination (HR). IP6K1 knock-out MEFs show decreased viability and reduced recovery after induction of DNA damage by the replication stress inducer, hydroxyurea, or the radiomimetic antibiotic, neocarzinostatin. Cells lacking IP6K1 arrest after genotoxic stress, and markers associated with DNA repair are recruited to DNA damage sites, indicating that HR repair is initiated in these cells. However, repair does not proceed to completion because these markers persist as nuclear foci long after drug removal. A fraction of IP6K1-deficient MEFs continues to proliferate despite the persistence of DNA damage, rendering the cells more susceptible to chromosomal aberrations. Expression of catalytically active but not inactive IP6K1 can restore the repair process in knock-out MEFs, implying that inositol pyrophosphates are required for HR-mediated repair. Our study therefore highlights inositol pyrophosphates as novel small molecule regulators of HR signaling in mammals.
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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.