The pathways leading to synthesis and post-synthetic modification of DNA employed methionine as donor of atoms: the carbon that came from its –CH3 served for DNA replication and repair either in bacteria or humans;it...The pathways leading to synthesis and post-synthetic modification of DNA employed methionine as donor of atoms: the carbon that came from its –CH3 served for DNA replication and repair either in bacteria or humans;its entire –CH3 served instead for building N6-methyladenine and 5-methylcytosine on bacterial DNA and 5-methylcytosine alone on human DNA. In humans, although a slight extra-S asymmetric methylation appeared de novo yielding on parental DNA 5’-m5CpC-3’/ 3’-GpG-5’, 5’-m5CpT-3’/3’-GpA-5’ and 5’-m5CpA-3’/3’-GpT-5’ monomethylated dinucleotide pairs, a heavy symmetric methylation involved in S semiconservatively newly made DNA to guarantee genetic maintenance of –CH3 in 5’-m5CpG-3’/3’-Gpm5C-5’ dimethylated dinucleotide pairs. In this framework, an inverse correlation was found between bulk genomic DNA methylation occurring in S and bulk polyA-containing pre-mRNA transcription taking place in G1 and G2. Thus, probes of 1 × 106 Daltons (constructed using sheared by sonication newly made methylated DNA filaments) revealed a modular organization in genes: after the hypermethylated promoter, they exhibited an alternation of unmethylated coding and methylated uncoding sequences. This encouraged the search for a language that genes regulated by methylation should have in common. An initial deciphering of restriction minimaps with hypomethylatable exons vs. hypermethylatable promoters and introns was improved when the bisulfite technique allowed a direct sequencing of m5C. In lymphocytes, where the transglutaminase gene is inactive, its promoter exhibited two fully methylated CpG-rich domains at 5’ and one fully unmethylated CpG-rich domain at 3’, including the site +1 and a 5’-UTR. At variance, in HUVEC cells, where the transglutaminase gene is active, in the first CpG-rich domain of promoter few doublets lost their –CH3. Such an inverse correlation suggested new hypotheses especially in connection with repair-modification: UV radiation would cause demethylation in given loci of a promoter by chance, whilst even a partial demethylation in this promoter would be able to resume a previously silent pre-mRNA transcription.展开更多
This survey points to the mechanisms of bioresponse caused by magnetic fields (MFs), paying attention to their action not only on ions, molecules and macromolecules, but also on cells, tissues and organisms. The signi...This survey points to the mechanisms of bioresponse caused by magnetic fields (MFs), paying attention to their action not only on ions, molecules and macromolecules, but also on cells, tissues and organisms. The significance of findings concerning the MF-dependence of cell proliferation, necrosis or apoptosis was judged by comparing the results obtained in a solenoid, where an MF can be added to the geomagnetic field (GMF), with those obtained in a magnetically shielded room, where the MFs can be attenuated or null. This comparative criterion was particularly appropriate when the differences detectable between the data provided by experimental samples and the data provided by control samples were rather small, as observed in estimating the MF-influence on total DNA replication, RNA transcription and polypeptide translation. The MF-induced inhibition of apoptosis was considered as a risk potentially leading to accumulation of cancer cells. The analysis also surveyed the MF-dependence of the interactions between host animal cells and infecting bacteria. In relation to studies on the origin and adaptation of life on the Earth, theoretical insights paving the way to elucidating the MF-interactions with biostructures and biosystems of different orders of organization evaluated the possible involvement of the so-called “biological windows”. Analogously to what is known for ionizing radiations, the efficiency of the applied MFs appeared to depend on the complexity of their biological targets.展开更多
文摘The pathways leading to synthesis and post-synthetic modification of DNA employed methionine as donor of atoms: the carbon that came from its –CH3 served for DNA replication and repair either in bacteria or humans;its entire –CH3 served instead for building N6-methyladenine and 5-methylcytosine on bacterial DNA and 5-methylcytosine alone on human DNA. In humans, although a slight extra-S asymmetric methylation appeared de novo yielding on parental DNA 5’-m5CpC-3’/ 3’-GpG-5’, 5’-m5CpT-3’/3’-GpA-5’ and 5’-m5CpA-3’/3’-GpT-5’ monomethylated dinucleotide pairs, a heavy symmetric methylation involved in S semiconservatively newly made DNA to guarantee genetic maintenance of –CH3 in 5’-m5CpG-3’/3’-Gpm5C-5’ dimethylated dinucleotide pairs. In this framework, an inverse correlation was found between bulk genomic DNA methylation occurring in S and bulk polyA-containing pre-mRNA transcription taking place in G1 and G2. Thus, probes of 1 × 106 Daltons (constructed using sheared by sonication newly made methylated DNA filaments) revealed a modular organization in genes: after the hypermethylated promoter, they exhibited an alternation of unmethylated coding and methylated uncoding sequences. This encouraged the search for a language that genes regulated by methylation should have in common. An initial deciphering of restriction minimaps with hypomethylatable exons vs. hypermethylatable promoters and introns was improved when the bisulfite technique allowed a direct sequencing of m5C. In lymphocytes, where the transglutaminase gene is inactive, its promoter exhibited two fully methylated CpG-rich domains at 5’ and one fully unmethylated CpG-rich domain at 3’, including the site +1 and a 5’-UTR. At variance, in HUVEC cells, where the transglutaminase gene is active, in the first CpG-rich domain of promoter few doublets lost their –CH3. Such an inverse correlation suggested new hypotheses especially in connection with repair-modification: UV radiation would cause demethylation in given loci of a promoter by chance, whilst even a partial demethylation in this promoter would be able to resume a previously silent pre-mRNA transcription.
文摘This survey points to the mechanisms of bioresponse caused by magnetic fields (MFs), paying attention to their action not only on ions, molecules and macromolecules, but also on cells, tissues and organisms. The significance of findings concerning the MF-dependence of cell proliferation, necrosis or apoptosis was judged by comparing the results obtained in a solenoid, where an MF can be added to the geomagnetic field (GMF), with those obtained in a magnetically shielded room, where the MFs can be attenuated or null. This comparative criterion was particularly appropriate when the differences detectable between the data provided by experimental samples and the data provided by control samples were rather small, as observed in estimating the MF-influence on total DNA replication, RNA transcription and polypeptide translation. The MF-induced inhibition of apoptosis was considered as a risk potentially leading to accumulation of cancer cells. The analysis also surveyed the MF-dependence of the interactions between host animal cells and infecting bacteria. In relation to studies on the origin and adaptation of life on the Earth, theoretical insights paving the way to elucidating the MF-interactions with biostructures and biosystems of different orders of organization evaluated the possible involvement of the so-called “biological windows”. Analogously to what is known for ionizing radiations, the efficiency of the applied MFs appeared to depend on the complexity of their biological targets.
