Biochemical and Biophysical Research Communications
Coordinate inhibition of DNA synthesis and thymidylate synthase activity following DNA damage and repair
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Folylpoly-ɣ-glutamate synthetase association to the cytoskeleton: Implications to folate metabolon compartmentalization
2021, Journal of ProteomicsCitation Excerpt :Apart from the binding of glycolytic enzymes to the cytoskeleton, several recent reports identified multimeric complexes of glycolytic enzymes near the PM of erythrocytes [172,173]. These reports, together with evidence of folate-dependent metabolons of multi-enzyme complexes participating in the biosynthesis of purines and thymidylate in the cytosol and nucleus, also known as purinosome [40,46,48–51,174], corroborated the possibility that cFPGS is part of a large enzyme complex that is microtubule bound, assembled by TRiC and regulated by 14-3-3 proteins. Additional interesting proteins that were found to immunoprecipitate with cFPGS include the T-complex protein 1 (TCP1) ring complex (TRiC) [152,153] and the family of 14-3-3 proteins.
Serum homocysteine, arsenic methylation, and arsenic-induced skin lesion incidence in Bangladesh: A one-carbon metabolism candidate gene study
2018, Environment InternationalCitation Excerpt :Elevated Hcys, an indicator of OCM dysregulation, was associated with skin lesion incidence independently of urinary %DMA, and the association of TYMS rs1001761 with increased skin lesion risk highlights the potential role of OCM in As toxicity independent of As methylation efficiency. The TYMS gene encodes for thymidylate synthetase (TS), which uses the MTHFR substrate 5,10-methylenetetrahydrofolate for the methylation of 2-deoxy-uridine-5-monophosphate (dUMP) to 2-deoxy-thymidine-5-monophosphate (dTMP) (Carreras and Santi, 1995) and is critical for DNA synthesis and repair (Boorstein and Pardee, 1983; Johnston et al., 1995). Given that the rs1001761 risk allele is associated with increased odds for skin lesions with higher As exposures (>50 μM), we hypothesize that DNA damage involving TS may be a mechanism of As toxicity at higher As concentrations.
NAD(P)H:quinone oxidoreductase 1 (NQO1) in the sensitivity and resistance to antitumor quinones
2012, Biochemical PharmacologyCitation Excerpt :β-lapachone was shown to have anti-bacterial and anti-fungal and anti-trypanosomal properties primarily due to the ability of β-lapachone to rapidly induce the formation of superoxide and hydrogen peroxide with the simultaneous oxidation of reduced pyridine nucleotides [70]. Early experiments demonstrated that β-lapachone could inhibit the repair of mammalian DNA through a mechanism involving inhibition of topoisomerase I [71–74]. β-lapachone has been shown to induce apoptosis in human leukemia and prostate cancer cells and over-expression of BCL2 could protect cells against β-lapachone induced apoptosis [75].
Chapter 1 Folate-Mediated One-Carbon Metabolism
2008, Vitamins and HormonesCitation Excerpt :The three enzymes that constitute the TS cycle [SHMT1, TS, and dihydrofolate reductase (DHFR)] are all substrates for UBC9‐mediated modification with the small ubiquitin‐like modifier (SUMO), which targets proteins for nuclear localization during S‐phase (Anderson et al., 2007; Woeller et al., 2007a). Nuclear TS was shown to form part of a putative “replitase complex” along with DNA polymerase α, ribonucleotide reductase, thymidylate kinase, NDP kinase, the folate‐dependent enzyme DHFR (Boorstein and Pardee, 1983; Noguchi et al., 1983; Prem veer Reddy and Pardee, 1980), and possibly SHMT1 (Woeller, 2007a). Because SHMT1 exhibits a narrow range of tissue‐specific expression compared with TS and DHFR, it is unlikely that all cells synthesize thymidylate in the nucleus.
Evidence for small ubiquitin-like modifier-dependent nuclear import of the thymidylate biosynthesis pathway
2007, Journal of Biological ChemistryCitation Excerpt :DNA polymerase α, ribonucleotide reductase, thymidine kinase, and NDP kinase were initially identified as replitase-associated proteins (49). Later, Pardee and co-workers (50, 51) identified dihydrofolate reductase (DHFR) and TS activity in purified replitase complexes. Others have found that the enzyme TS localizes to the nuclear periphery but not the nucleus in Saccharomyces cerevisiae, whereas it localizes to the nucleus of colorectal cancer cell lines (52, 53).
Inhibition of poly(ADP-ribose) polymerase activation attenuates β-lapachone-induced necrotic cell death in human osteosarcoma cells
2002, Toxicology and Applied Pharmacology
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