https://www.mun.ca/biology/scarr/Jacob_&_Monod_(1961)_presentation.pdf

Genetic regulatory mechanisms in the synthesis of proteins.

DNA cytosine methylation is crucial for retrotransposon silencing and mammalian development. In a computational search for enzymes that could modify 5-methylcytosine (5mC), we identified TET proteins as mammalian homologs of the trypanosome proteins JBP1 and JBP2, which have been proposed to oxidize the 5-methyl group of thymine. We show here that TET1, a fusion partner of the MLL gene in acute myeloid leukemia, is a 2-oxoglutarate (2OG)- and Fe(II)-dependent enzyme that catalyzes conversion of 5mC to 5-hydroxymethylcytosine (hmC) in cultured cells and in vitro. hmC is present in the genome of mouse embryonic stem cells, and hmC levels decrease upon RNA interference–mediated depletion of TET1. Thus, TET proteins have potential roles in epigenetic regulation through modification of 5mC to hmC.

/pdf/conversion-of-5-methylcytosine-to-5-hydroxymethylcytosine-in-30xwwwwmf6.pdf

Conversion of 5-Methylcytosine to 5-Hydroxymethylcytosine in Mammalian DNA by MLL Partner TET1

The study of the growth of bacterial cultures does not constitute a specialized subject or branch of research: it is the basic method of Microbiology. It would be a foolish enterprise, and doomed to failure, to attempt reviewing briefly a \"subject\" which covers actually our whole discipline. Unless, of course, we considered the formal laws of growth for their own sake, an approach which has repeatedly proved sterile. In the present review we shall consider bacterial growth as a method for the study of bacterial physiology and biochemistry. More precisely, we shall concern ourselves with the quantitative aspects of the method, with the interpretation of quantitative data referring to bacterial growth. Furthermore, we shall considerz exclusively the positive phases of growth, since the study of bacterial \"death,\" i.e., of the negative phases of growth, involves distinct problems and methods. The discussion will be limited to populations considered genetically homogeneous. The problems of mutation and selection in growing cultures have been excellently dealt with in recent review articles by Delbriick (1) and Luria (2). No attempt is made at reviewing the literature on a subject which, as we have just seen, is not really a subject at all. The papers and results quoted have been selected as illustrations of the points discussed.

The Growth of Bacterial Cultures

Despite the importance of epigenetic regulation in neurological disorders, little is known about neuronal chromatin. Cerebellar Purkinje neurons have large and euchromatic nuclei, whereas granule cell nuclei are small and have a more typical heterochromatin distribution. While comparing the abundance of 5-methylcytosine in Purkinje and granule cell nuclei, we detected the presence of an unusual DNA nucleotide. Using thin-layer chromatography, high-pressure liquid chromatography, and mass spectrometry, we identified the nucleotide as 5-hydroxymethyl-2′-deoxycytidine (hmdC). hmdC constitutes 0.6% of total nucleotides in Purkinje cells, 0.2% in granule cells, and is not present in cancer cell lines. hmdC is a constituent of nuclear DNA that is highly abundant in the brain, suggesting a role in epigenetic control of neuronal function.

/pdf/the-nuclear-dna-base-5-hydroxymethylcytosine-is-present-in-1z2hf1arc8.pdf

The Nuclear DNA Base 5-Hydroxymethylcytosine Is Present in Purkinje Neurons and the Brain

Phosphorus compounds in animal tissues; extraction and estimation of desoxypentose nucleic acid and of pentose nucleic acid.

https://www.pnas.org/content/pnas/44/10/1004.full.pdf

The mode of action of 5-fluorouracil and its derivatives.

/pdf/the-bases-of-the-nucleic-acids-of-some-bacterial-and-animal-39vgp0pe2v.pdf

The bases of the nucleic acids of some bacterial and animal viruses: the occurrence of 5-hydroxymethylcytosine.

Summary The 5′-triphosphate of 1-β-d-arabinofuranosylcytosine (ara-CTP) was tested as a substrate or inhibitor of polynucleotide synthesis using mammalian polymerases. The compound did not replace deoxycytidine triphosphate (dCTP) as substrate for DNA polymerase and did not replace cytidine triphosphate as substrate for RNA polymerase. The compound was found to inhibit DNA synthesis catalyzed by DNA polymerase; the inhibition appeared to be competitive with dCTP. No inhibition of RNA polymerase was observed. Further studies indicate that the inhibition of mammalian DNA polymerase by the 5′-triphosphate of 9-β-d-arabinofuranosyladenine (ara-ATP) is also competitive with the corresponding deoxytriphosphate. The data on the mode of action of 1-β-d-arabinofuranosylcytosine and of 9-β-d-arabinofuranosyladenine have been summarized, and the present status of hypotheses on these mechanisms have been discussed. The data are consistent with the view that ara-CTP and ara-ATP act in animal cells via their respective triphosphates to inhibit the animal cell DNA polymerase, although ara-ATP, but not ara-CTP, may also act by inhibiting ribonucleotide reductase.

https://cancerres.aacrjournals.org/content/canres/28/10/2061.full.pdf

Inhibition of mammalian DNA polymerase by the 5'-triphosphate of 1-beta-d-arabinofuranosylcytosine and the 5'-triphosphate of 9-beta-d-arabinofuranoxyladenine.

Studies on unbalanced growth in escherichia coli.

THE pyrimidine cytosine1 and its deoxynucleotide2 have been reported as constituents of the deoxyribonucleic acids of coliphages T2 and T6 respectively, but in another analysis of T23 no cytosine could be found. We have now resolved this discrepancy by isolation from T-even bacteriophages of a new pyrimidine base, identified as 5-hydroxymethyl-cytosine, which was previously mistaken for cytosine or missed. A nucleotide has now also been isolated which gives rise to this base on hydrolysis4.

Seymour S. Cohen

Papers

The mode of action of 5-fluorouracil and its derivatives.

The bases of the nucleic acids of some bacterial and animal viruses: the occurrence of 5-hydroxymethylcytosine.

Inhibition of mammalian DNA polymerase by the 5'-triphosphate of 1-beta-d-arabinofuranosylcytosine and the 5'-triphosphate of 9-beta-d-arabinofuranoxyladenine.

Studies on unbalanced growth in escherichia coli.

A New Pyrimidine Base from Bacteriophage Nucleic Acids