ArticleActa neuropathologica2022
DTYMK is essential for genome integrity and neuronal survival.
Article in Acta neuropathologica, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- Multi-omics analysis revealed coordinated responses of rumen microbiota and epithelium of goats to dietary supplementation of glucosamine selenium.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2025Article
- Construction of a novel G2/M checkpoint-related gene signature for prognosis in hepatocellular carcinoma based on machine learning.Discover oncology · 2025Article
- Characterization of dUTPase expression in mouse postnatal development and adult neurogenesis.Scientific reports · 2024Article
- DTYMK is an essential gene in mice and heterozygosity does not cause neural tube defects.Archives of biochemistry and biophysics · 2024Article
- Debaryomyces hansenii supplementation in low fish meal diets promotes growth, modulates microbiota and enhances intestinal condition in juvenile marine fish.Journal of animal science and biotechnology · 2023Article
- The evolving landscape of involvement of DTYMK enzymes in cancer.Medical oncology (Northwood, London, England) · 2023Review
- Comprehensive analysis of DTYMK in pan-cancer and verification in lung adenocarcinoma.Bioscience reports · 2022Article
- Article
- Differential expression of enzymes in thymidylate biosynthesis in zebrafish at different developmental stages: implications for dtymk mutation-caused neurodegenerative disorders.BMC neuroscience · 2022Article
- Targeting theFrontiers in cellular and infection microbiology · 2022Article
- Article
- The Biological Behavior and Clinical Application Prospects of Deoxythymidine Kinase Gene in Tumors.Technology in cancer research & treatmentReview
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Authors and funding
20 authors at 7 institutions in 5 countries.
Funding
Abstract
Nucleotide metabolism is a complex pathway regulating crucial cellular processes such as nucleic acid synthesis, DNA repair and proliferation. This study shows that impairment of the biosynthesis of one of the building blocks of DNA, dTTP, causes a severe, early-onset neurodegenerative disease. Here, we describe two unrelated children with bi-allelic variants in DTYMK, encoding dTMPK, which catalyzes the penultimate step in dTTP biosynthesis. The affected children show severe microcephaly and growth retardation with minimal neurodevelopment. Brain imaging revealed severe cerebral atrophy and disappearance of the basal ganglia. In cells of affected individuals, dTMPK enzyme activity was minimal, along with impaired DNA replication. In addition, we generated dtymk mutant zebrafish that replicate this phenotype of microcephaly, neuronal cell death and early lethality. An increase of ribonucleotide incorporation in the genome as well as impaired responses to DNA damage were observed in dtymk mutant zebrafish, providing novel pathophysiological insights. It is highly remarkable that this deficiency is viable as an essential component for DNA cannot be generated, since the metabolic pathway for dTTP synthesis is completely blocked. In summary, by combining genetic and biochemical approaches in multiple models we identified loss-of-function of DTYMK as the cause of a severe postnatal neurodegenerative disease and highlight the essential nature of dTTP synthesis in the maintenance of genome stability and neuronal survival.
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