The effect of methotrexate (MTX) on thymidylate syn thetase activity during liver regeneration was examined with parenchymal cells isolated 22 and 44 hr after partial hepatectomy and cultured as a monolayer. The synthetase activity in these cells decreased with a half-life of 18 to 24 hr. but if MTX (1.5 x l0' to 1.5 x l0@ M) was present in the culture media, this decline could be delayed for a...

Experimental evidence for a 5-exocyclic methylene-dUMP intermediate in the thymidylate synthase reaction was recently obtained by demonstrating that tryptophan 82 mutants of the Lactobacillus casei enzyme produced 5-(2-hydroxyethyl)thiomethyl-dUMP (HETM-dUMP) (Barret, J. E., Maltby, D. A., Santi, D. V., and Schultz, P. G. (1998) J. Am. Chem. Soc. 120, 449-450). The unusual product was proposed ...

When the nonprotein chromophore of neocarzinostatin was allowed to react with either calf thymus DNA or poly(dA-dT) . poly(dA-dT) in the presence of 2-mercaptoethanol and the DNA was precipitated with ethanol, 5% of the fluorescence attributable to the naphthalene rings of the chromophore coprecipitated with the DNA. Most of this fluorescence remained attached to DNA through successive reprecip...

Thymidylate synthase (TS) is the only de novo source of thymidylate (dTMP) for DNA synthesis and repair. Drugs targeting TS protein are a mainstay in cancer treatment, but off-target effects and toxicity limit their use. Cytosolic thymidine kinase (TK1) and mitochondrial thymidine kinase (TK2) contribute to an alternative dTMP-producing pathway, by salvaging thymidine from the tumor milieu, and...

We investigated the capabilities of a canopy height model (CHM) derived from aerial photographs using the Structure from Motion (SfM) approach to estimate aboveground biomass (AGB) in a tropical forest. Aerial photographs and airborne Light Detection and Ranging (LiDAR) data were simultaneously acquired under leaf-on canopy conditions. A 3D point cloud was generated from aerial photographs usin...

Dynamical modeling is an accurate tool for describing the dynamic regulation of one-carbon metabolism (1CM) with emphasis on the alteration of DNA methylation and/or dUMP methylation into dTMP. Using logic programming we present a comprehensive and adaptative mathematical model to study the impact of folate deficiency, including folate transport and enzymes activities. 5-Methyltetrahydrofolate ...

Thymidylate kinase (TMK) catalyses the phosphorylation of dTMP to form dTDP in both the de novo and salvage pathways of dTTP synthesis. The tmk gene from the bacterial pathogen Streptococcus pneumoniae was identified. The gene, encoding a 212-amino-acid polypeptide (23352 Da), was cloned and overexpressed in Escherichia coli with an N-terminal hexahistidine tag. The enzyme was purified to homog...

The phagosomal transporter (Pht) family of the major facilitator superfamily (MFS) is encoded by phylogenetically related intracellular gammaproteobacteria, including the opportunistic pathogen Legionella pneumophila. The location of the pht genes between the putative thymidine kinase (tdk) and phosphopentomutase (deoB) genes suggested that the phtC and phtD loci contribute to thymidine salvage...

This article has been published as a correction for an error in the manuscript of Pavlov et al BMC Biology 2004, 2:11. This article has been published as a correction for [1]. The legend for figure 2 in the original article states, "(C) Plot of time-course of DNA synthesis and dTMP turnover by wild-type Pol e. Open circles connected by solid line represent dTMP retained into DNA; open rectangle...

Dihydrofolate reductase (DHFR; tetrahydrofolate; NADP' oxidoreductase, EC 1.5.1.3) catalyses the NADPH-dependent reduction of 7,8-dihydrofolate (FAH,) to 5,6,7,8-tetrahydrofolate (FAH,). The coenzyme FAH, serves as a carrier of one-carbon fragments in a number of biosynthetic transfer reactions (Rader & Huennekens, 1973). It is apparent that DHFR is the intracellular target for the anti-cancer ...