DNA (deoxyribonucleic acid) is a nucleic acid that encodes the genetic information (genome) necessary for RNA (ribonucleic acid) transcription (transcriptome) and protein synthesis (proteome) 1. It is contained in the nucleus of eukaryotic cells in the form of chromatin or chromosomes 7,8. Human DNA is characterised by numerous interindividual variations: genes, in fact, also act in a probabilistic and not just deterministic way in defining a phenotype 23. Furthermore, because only about 2% of the human genome contains protein coding sequences, the rest had been defined as “junk DNA” 24 but is now understood to have various important roles including that it is transcribed into different types of non-coding RNAs 25.
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Molecular structure
DNA is made up of two double-stranded polynucleotide chains. Each nucleotide consists of a pentose, 2-deoxy-D-ribose, to which the nitrogenous base and a phosphate group are covalently linked (N-glycosidic and phosphoester respectively). The nucleotides, in turn, are held together by "bridging" chemical bonds between the pentose molecules (phosphodiesteric chemical bond) 2,3.
The two polynucleotide chains, on the other hand, are joined by hydrogen bonds (H-bonds); they are established between the complementary heterocyclic base pairs: two H-bonds between adenine (A) and thymine (T) and three H-bonds between guanine (G) and cytosine (C) 4.
Primary structure
The primary structure is the sequence of heterocyclic bases along the polynucleotide chain that characterise the DNA 2.
Secondary structure
The secondary structure equates to the right-handed double helix proposed in 1953 by James D Watson and Francis H Crick (B-form) for which they won the Nobel Prize 3. Each complete turn of the double helix takes ten pairs of nucleotides 6.
Epigenetics
It is the branch of genetics that studies all the heritable modifications that vary the gene expression (phenotype) while not altering the DNA sequence 13-15.
DNA methylation
DNA methylation is the process whereby specific regions of DNA can be altered by the addition of methyl groups (-CH3). This is an epigenetic mechanism used by the human cell to modulate gene expression and can be assessed using DNA methylation profiling.
Practical applications
Circulating tumour DNA
Circulating tumour DNA (ctDNA) are fragments of DNA released into the blood by cancer cells. The possibility of sequencing and monitoring it is the basis of diagnostic techniques known as "liquid biopsy" 9.
Polymerase chain reaction
Polymerase chain reaction (PCR) is a molecular biology technique to multiply copies of DNA and quantify potential genomes present in a given sample preparation 10. The technique was developed by K B Mullis, Nobel Prize in Chemistry in 1993. In the specific case of RNA sequences, these must first be reverse-transcribed into DNA (RT-PCR) 11.
Radiolabeled nitrogen bases
Some nitrogenous bases constituting the nucleic acids, if radiolabeled (for example 5 [125I] -2'-deoxyuridine) can be used, in vitro or in vivo, to estimate the extent of cell proliferation in oncology 12.
Gene editing
Gene editing technologies allow precise modifications in DNA; among these, CRISPR-Cas9 technology (and its evolutions, CRISPR-Cas12,13 and 14) stands out for its efficiency and versatility. CRISPR (clustered regularly interspaced short palindromic repeats) uses an RNA guide to direct the Cas9 enzyme towards specific DNA sequences, allowing their modification or removal. Although the applications of gene editing are promising, they impose important ethical considerations 26-30.
History and etymology
The discovery of DNA as a chemical substance dates back to 1869; It was Friedrich Miescher, a Swiss biologist, who studied the basic chemistry of deoxyribunucleic acid, demonstrating how the chromosomes (of the nuclei of white blood cells) were essentially made up of this macromolecule, which he called "nuclein" 16,17.
In the early fifties, Erwin Chargaff, a biochemist at Columbia University (USA) observed some regularities in the distribution of the nitrogenous bases that make up double-stranded DNA: the percentages of adenine and thymine are equivalent as are those of guanine and cytosine (Chargaff first parity rule). It was precisely this pairing rule that was the basis of the double helix model proposed by Watson and Crick in 1953 19-21.
Rosalind Franklin of King's College in London was the scientist who first managed to "photograph" a DNA molecule in the so-called photograph 51, which allowed us to understand the true 3D-structure of the molecule custodian for the code of life (1952) 18,22.
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