Search results for "Nucleotidyltransferases"

PARP inhibition enhances tumor cell-intrinsic immunity in ERCC1-deficient non-small cell lung cancer.

2018

The cyclic GMP-AMP synthase/stimulator of IFN genes (cGAS/STING) pathway detects cytosolic DNA to activate innate immune responses. Poly(ADP-ribose) polymerase inhibitors (PARPi) selectively target cancer cells with DNA repair deficiencies such as those caused by BRCA1 mutations or ERCC1 defects. Using isogenic cell lines and patient-derived samples, we showed that ERCC1-defective non-small cell lung cancer (NSCLC) cells exhibit an enhanced type I IFN transcriptomic signature and that low ERCC1 expression correlates with increased lymphocytic infiltration. We demonstrated that clinical PARPi, including olaparib and rucaparib, have cell-autonomous immunomodulatory properties in ERCC1-defecti…

YAP/TAZ activity in stromal cells prevents ageing by controlling cGAS-STING

2022

Ageing is intimately connected to the induction of cell senescence(1,2), but why this is so remains poorly understood. A key challenge isthe identification of pathways that normally suppress senescence, are lost during ageing and are functionally relevant to oppose ageing(3). Here we connected the structural and functional decline of ageing tissues to attenuated function of the master effectors of cellular mechanosignalling YAP and TAZ. YAP/TAZ activity declines during physiological ageing in stromal cells, and mimicking such decline through genetic inactivation of YAP/TAZ in these cells leads to accelerated ageing. Conversely, sustaining YAP function rejuvenates old cells and opposes the e…

Biological Activity of the phenylethanol and its derivatives. Influence on isolated DNA nucleotidyltransferase and DNAase.

1970

Intracellular location of DNA nucleotidyltransferase.

1962

Inhibitors acting on nucleic acid synthesis in an oncogenic RNA virus.

1971

IN infection with an oncogenic RNA virus, synthesis of viral RNA seems to be catalysed by an RNA dependent DNA polymerase in the host cell1–4. Several specific inhibitors of viral DNA polymerases have been found5–7 and Spiegelman8 has shown that the activity of viral enzymes depends strongly on the chemical composition of the template. We report here first a new highly specific poison of the Rauscher murine leukaemia virus (RMLV) DNA polymerases; second, several inactivators of the RNA and DNA template involved in the RMLV enzyme systems; and third, the action of actinomycin D on viral DNA polymerases and on host DNA/RNA polymerase. The results are discussed with respect to the influence of…

A Sensitive Method for Identification of DNA Dependent DNA Polymerases in Acrylamide Gels after Seperation by Micro Disc Electrophoresis

1973

Abstract DNA polymerase, disc electrophoresis, template affinity Two sensitive methods are described for detection of DNA dependent DNA polymerase activities in polyacrylamide gels after their fractionation by micro-disc electrophoresis. One technique is based on the increase in fluorescence of the ethidium bromide complex with template polydeoxyribonucleotides brought about by the action of the polymerases. The sensitivity of the previously described technique has been enhanced. Another method, 14 fold as sensitive, uses radioactive precursors in the enzyme assay after electrophoretic separation; washing, slicing and counting allows to evaluate incorporation into acid insoluble polymer, re…

Of mice and models: improved animal models for biomedical research.

2002

The ability to engineer the mouse genome has profoundly transformed biomedical research. During the last decade, conventional transgenic and gene knockout technologies have become invaluable experimental tools for modeling genetic disorders, assigning functions to genes, evaluating drugs and toxins, and by and large helping to answer fundamental questions in basic and applied research. In addition, the growing demand for more sophisticated murine models has also become increasingly evident. Good state-of-principle knowledge about the enormous potential of second-generation conditional mouse technology will be beneficial for any researcher interested in using these experimental tools. In thi…

Age-dependent alterations of DNA synthesis. Terminal deoxynucleotidyl transferase and DNA polymerase activities in bone marrow subpopulations from mi…

1980

Abstract The decrease of functional capacity of cellular immunity during ageing seems to be due to cellular changes of stem cells, particularly in the growth properties and the cell density in T-cell subsets. We approached this problem at the molecular biological level by quantifying the key enzymes necessary for DNA synthesis in bone marrow cells from mice: deoxynucleotidyl transferase (TdT) and DNA polymerase α. The bone marrow cells were fractionated on a discontinuous bovine serum albumin density gradient and the extractable enzyme activities (expressed per 10 8 nucleated cells in the respective fraction) were determined. TdT activity was found to decrease markedly during ageing. Mature…

Bleomycin inhibition of DNA synthesis in isolated enzyme systems and in intact cell systems.

1975

Abstract Blcomycin (BLM) inhibits DNA and RNA synthesis in different isolated enzyme systems. The inhibition effect can be reduced by adcling RNA to the reaction mixture. The activity of the RNA dependent DNA polymerase and of a cell-free protein synthesizing system is not affected by BLM. The antibiotic reduces cell proliferation (L5178y mouse lymphoma cells) in vitro at low concentrations by cytostatis and at higher concentrations by cytotoxicity. In BLM-treated L5178y cells DNA synthesis is strongly reduced, while RNA and protein synthesis are not affected. In vivo , using growing quail oviducts, cell proliferation and cytodifferentiation are markedly inhibited after BLM treatment. This …

The mitochondrial genome of Schizosaccharomyces pombe. Stimulation of intra-chromosomal recombination in Escherichia coli by the gene product of the …

1991

The open reading frame of the first intron of the mitochondrial cox1 gene (cox1I1) was expressed in Escherichia coli. The putative intron-encoded protein stimulated the formation of intra-chromosomal lac +-recombinants about threefold. No stimulation was found when the reading frame was inserted in the opposite direction, or when it was interrupted by a deletion. The intronic open reading frame did not complement recA − or recB − mutants of E. coli. In S. pombe, elimination of this intron did not abolish homologous recombination in mitochondria. A possible role of the recombinase activity in yeast mitochondria will be discussed.