Thymidine kinase catalyzes the first step in the nucleotide salvage pathway by transferring a phosphate group to a thymidine molecule. In mammals thymidine kinase supplies deoxyribonucleotides for DNA replication and DNA repair, and the expression of the gene is tightly regulated during the cell cycle. Although this gene is phylogenetically conserved in many taxa, its physiological function in plants remains unknown. The genome of the model plant Arabidopsis thaliana has two thymidine kinase genes (AtTK1a and AtTK1b) and microarray data suggest they might have redundant roles. In this study we analyzed the TK1a function by evaluating its expression pattern during development and in response to genotoxic stress. We also studied its role in DNA repair by the characterization of a mutant that contained the T-DNA insertion in the promoter region of the TK1a gene. We found that TK1a is expressed in most tissues during plant development and it was differentially induced by ultraviolet-C radiation because TK1b expression was unaffected. In the mutant, the T-DNA insertion caused a 40 % rise in transcript levels and enzyme activity in Arabidopsis seedlings compared to wild-type plants. This elevation was enough to confer tolerance to ultraviolet-C irradiation in dark conditions, as determined by root growth, and meristem length and structure. TK1a overexpression also provided tolerance to genotoxins that induce double-strand break. Our results suggest that thymidine kinase contributes to several DNA repair pathways by providing deoxythymidine triphosphate that serve as precursors for DNA repair and to balance deoxyribonucleotides pools.
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http://dx.doi.org/10.1007/s11103-014-0277-7 | DOI Listing |
World J Oncol
February 2025
The First Clinical Medical School, Jinan University, Guangzhou 510632, Guangdong, China.
Background: Thymidine kinases (TKs) are key enzymes involved in DNA synthesis and repair, with alterations in their expression associated with various cancers. Thymidine kinase 1 (TK1) and TK2 are cytosolic enzyme proteins that catalyze the addition of a gamma-phosphate group to thymidine. The existing literature on TK1 in cervical squamous cell carcinoma (CESC) fails to address the clinical role of TK1 overexpression and its possible molecular mechanism in CESC.
View Article and Find Full Text PDFNat Struct Mol Biol
January 2025
Zhejiang Provincial Key Laboratory of Pancreatic Disease, Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Thymidine kinase 1 (TK1), a crucial enzyme in DNA synthesis, is highly expressed in various cancers. However, the mechanisms underlying its elevated expression and the implications for tumor metabolism remain unclear. Here we demonstrate that activation of growth factor receptors enhances TK1 expression.
View Article and Find Full Text PDFAnn Med
December 2025
Department of Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.
Background: We previously described the enrichment of plasma exosome metabolites in CRPC, PCa, and TFC cohorts, and found significant differences in pyrimidine metabolites. The PMGs is associated with the clinical prognosis of several cancers, but its biological role in PCa is still unclear.
Methods: This study extracted 98 reliable PMGs, and analyzed their somatic mutations, expression levels, and prognostic significance.
Viruses
November 2024
Department of Virology 1, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
Herpes simplex virus type 1 (HSV-1) acyclovir (ACV) resistance is acquired by mutations in the viral thymidine kinase (TK) or DNA polymerase (DNApol) genes. We previously obtained an ACV-resistant clone (HSV-1_VZV_TK_clone α) by sequential passages of HSV-1_VZV-TK, a recombinant virus which lacked its endogenous TK activity and instead expressed the varicella-zoster virus (VZV) TK ectopically. HSV-1_VZV_TK_clone α had been generated using an HSV-1_BAC in the presence of increasing concentrations of ACV.
View Article and Find Full Text PDFAcad Radiol
January 2025
Department of Radiology, Shengjing Hospital of China Medical University, China (Y.Y., T.W.). Electronic address:
Rationale And Objectives: Mixed ground-glass nodules (mGGNs) are highly malignant and common nonspecific lung imaging findings. This study aimed to explore whether combining quantitative and qualitative spectral dual-layer detector-based computed tomography (SDCT)-derived parameters with serological tumor abnormal proteins (TAPs) and thymidine kinase 1 (TK1) expression enhances invasive mGGN diagnostic efficacy and to develop a joint diagnostic model.
Materials And Methods: This prospective study included patients with mGGNs undergoing preoperative triple-phase contrast-enhanced SDCT with TAP and TK1 tests.
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