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PubMed1976

DNA-histones, a computer model.

The model of DNA-histones has the following elements: 1. The hydrogen bonds between the complementary nucleotide bases function as informational gates. When the electrons pi of one nucleotide base are excited, an exchange of protons is produced between the two complementary bases. The result is the displacement of the conjugated double bonds which facilitates the inter-molecular transmission of the electronic wave of excitation by electro-magnetic coupling. 2. Each triplet of nucleotide bases of DNA fixes one definite amino acid (as in the genetic code). Between the nucleotide bases and the amino acids there are constituted informational gates, which ensure the circulation of the electronic wave of excitation. 3. An input signal molecule arrives at the receiver gene and unleashes the activity of the enzymes which introduce in the DNA-histones system the electronic wave of excitation. The electronic wave of excitation arises as a result of the break of the high-energy bonds of ATP. Then, the electronic excitation is transmitted to the productor gene where it represents the signal for starting the synthesis of the mRNA.

Adenosine Triphosphate↗
PubMed1987

Chemical xenogenization of experimental tumors.

Chemical xenogenization occurs when experimental tumors, treated in vivo or in vitro with selected chemicals, become immunogenic, i.e., able to induce a strong rejection response, immunological in nature, in the histocompatible hosts. Unlike modifications induced by haptens, changes in tumor cell immunogenicity associated with chemical xenogenization are heritable as a result of drug interference with the genetic code. Drugs endowed with potent mutagenic activity are known to be powerful xenogenizing agents, and their mechanism of action is traditionally regarded as involving changes in DNA nucleotide sequence. Triazene and nitrosoguanidine derivatives are among the best known examples of this type of compound, and a large body of information has been accumulated over the years regarding the immunogenic properties of the tumor variants obtained following treatment with those xenogenizing agents. The present paper reviews this information, and also discusses the therapeutic implications of xenogenization in experimental systems of tumor immunotherapy. Xenogenization of murine tumors has also been obtained by means of chemicals devoid of mutagenic activity but capable of affecting gene transcriptional activity. The characteristics of this 'new' type of xenogenization are also reviewed and compared to those of triazene xenogenization.

Animals↗
PubMed1995

Nucleic acid-binding metabolic enzymes: living fossils of stereochemical interactions?

Recently, a series of intriguing observations expanded the list of a number of metabolic enzymes known to be associated with various forms of nucleic acids, including single- and double-stranded DNA, cognate and noncognate RNAs, and specific tRNAs. There is no clear reason why such a phenomenon should take place in contemporary cell physiology, or, further, why such a property has evolved at all. Sixteen known cases are presented in an attempt to delineate any common features of these enzymes. Apart from their ancient nature, as judged by their wide distribution and their participation in fundamental biochemical pathways, it appears that these enzymes do not share any structural or functional characteristics. Given that most of these proteins require nucleotide-based cofactors for their activity, it is proposed that they may represent genuine molecular fossils of the transition from an RNA to a protein world. Their nucleic acid-binding properties are in keeping with previously proposed hypotheses regarding the origins and evolution of nucleotide-based cofactors. The mode of interaction between these proteins and their nucleic acid substrates remains unclear, but it may represent an extended form of stereochemical interactions that have been proposed for the origins of the genetic code.

Animals↗
PubMed1993

Origin of glutaminyl-tRNA synthetase: an example of palimpsest?

Sequence data and evolutionary arguments suggest that a similarity may exist between the C-terminal end of glutaminyl-tRNA synthetase (GlnRS) and the catalytic domain of glutamine amidotransferases (GATs). If true, this would seem to imply that the amidation reaction of the Glut-tRNA(Gln) complex was the evolutionary precursor of the direct tRNA(Gln) aminoacylation pathway. Since the C-terminal end of GlnRS does not now have an important functional role, it can be concluded that this sequence contains vestiges that lead us to believe that it represents a palimpsest. This sequence still conserves the remains of the evolutionary transition: amidation reaction-->aminoacylation reaction. This may be important in deciding which mechanism gave origin to the genetic code organization. These observations, together with results obtained by Gatti and Tzagoloff [J. Mol. Biol. (1991) 218:557-568], lead to the hypothesis that the class I aminoacyl-tRNA synthetases (ARSs) may be homologous to the GATs of the trpG subfamily, while the class II ARSs may be homologous to the GATs of the purF subfamily. Overall, this seems to point to the existence of an intimate evolutionary link between the proteins involved in the primitive metabolism and aminoacyl-tRNA synthetases.

Amino Acid Sequence↗
PubMed1994

Synonymous substitutions are clustered in enterobacterial genes.

The spatial distribution of synonymous substitutions in enterobacterial genes is investigated. It is shown that synonymous substitutions are significantly clustered in such a way that a synonymous substitution in one codon elevates the rate of synonymous substitution in an adjacent codon by about 10%. The level of clustering does not appear to be related to the level of gene expression, and it is restricted to a range of two or three codons. There are at least three possible explanations: (1) sequence-directed mutagenesis, (2) recombination, and (3) selection.

Base Sequence↗
PubMed1985

The development of biochemistry in the 20th century.

This lecture consists of a short appraisal of some of the main features that have characterized the growth of biochemistry during the course of the 20th century. It dwells on the early impacts of vitalism, the emergence and elucidation of the vitamins, the discovery of coenzymes, the concept of active centres of enzymes, the development of experimental techniques (including the use of isotopes), the genetic code, and on the development of molecular biology and closely allied fields of investigation. It concludes with a consideration of the influence of the study of membranes and of neurochemistry on current biochemical thought.

Animals↗
PubMed1979

The control region of the F sex factor DNA transfer cistrons: physical mapping by deletion analysis.

A technique has been developed which allows the isolation of random deletions extending from unique restriction enzyme sites in plasmid DNA molecules. The method involves transformation of E. coli cells with linear plasmid DNAs generated by restriction enzyme cleavage. We have used this technique to map DNA transfer genes in the tra control region of F sex factor DNA. Deletions within EcoRI fragment f6 of F DNA have been isolated and used to assign physical locations to tra genes by a combination of genetic complementation tests, restriction enzyme analysis, DNA heteroduplexing and the analysis of the proteins synthesised in minicells and in vitro. Deletion analysis has also allowed the identification of the traK gene product.

Bacterial Proteins↗