Tuesday, May 2, 2017

Genetics (5/8): The Molecular Fundamentals of Heredity

dna
After Morgan's discovery, many tried to determine if DNA or proteins, the genetic material of chromosomes.
In 1928 Griffith studied the bacteria and discovered the phenomenon of transformation, a variation of the genotype and phenotype linked to the assimilation of foreign DNA by a cell.
Avery in 1944 claimed that the transformed agent was DNA, but his discovery was met with skepticism, as many believed that proteins were the genetic material of excellence.
In 1952, Hershey and Chase studying bacteriophages claimed that DNA was the genetic material of the T2 bacterium, which was capable of reprogramming the cell to make it produce other viruses, and experimented with their theory by using radiotomized isotopes to mark DNA, Demonstrating that proteins did not come into play in this genetic transmission process.
Other tests are related to DNA distribution during mitosis, and Chargaff in 1947 demonstrated the DNA composition (the nitrogen base is always equal cmq: Adenina A, Timina T, Guanina G, Citosina C) ranges from one species to another .
Moreover, Chargaff discovered the equalities A = T and G = C common to all DNA molecules, now known as Chargaff's rules.
The final test was given by Watson and Crick who discovered in 1953 the double-helix DNA structure thanks to X-ray crystallography by the scholar Rosalind Franklin.
These scholars discovered that the DNA propeller runs a full turn every 3.4nm in terms of its length, and that the nitrogen bases were pegged so that adenine was with quinine and guanine with cytosine.
Adenine and guanine are purines, nitrogenous bases with 2 organic rings, while cytosine and thymine are pyrimidines, single-ring bases.
Hence adenine forms 2 hydrogen bonds only with thymine and guanine forms 3 hydrogen bonds only with cytosine.
The amount of guanine is thus equal to that of cytosine and adenine to thymine, and the linear sequence of the 4 bases can be varied infinitely, and each gene has a single order or sequence of bases.


Replication and DNA repair


The semiconservative model of Watson and Crick predicts that when the double helix is ​​duplicated, each of the daughters molecules is part of the old parent molecule and a new part.
Each of the human cells has about 6 billion pairs of bases, although a cell takes a few hours to copy all of its DNA and this replication is performed with very few errors, about one every billion nucleotides.

DNA replication begins at sites of said replication origins, where proteins bind to DNA by separating the two filaments and opening a replication bubble.
Replication proceeds in both directions until the entire molecule is copied.
At the end of a replication bubble there is a replenishing force, a Y-shaped region where new DNA filaments stretch.
This elongation is catalyzed by DNA polymerase enzymes that binds the nucleotides paired to the base at the expanding end of the new filament at a rate of about 50 nucleotides per second in human cells.
Polymerase DNA adds nucleotides in the free end of an increasing DNA strand but not in the 5 'end and therefore a new DNA strand may stretch only in the 5' to 3 'direction.
The polymerase positions itself in the molding force of a mold filament and continuously adds nucleotides to the complementary filament as the force extends and the filament formed with this mechanism is referred to as the filament guide.
To lengthen the other new filament, the polymerase must work on the other mold in the direction away from the force, and the DNA synthesized in this direction is referred to as a delayed filament.
The polymerase molecule moves away from the replication bubble when it opens, and replicates a short segment of DNA.
The delayed filament is initially synthesized as a set of short segments called Okazaki fragments.
The DNA ligase enzyme joins the sugar-phosphate skeletons of Okazaki fragments to generate a single DNA strand.
Polymerase DNA can not initiate the synthesis of a polynucleotide filament, it can only add nucleotides at the 3 'end of a pre-existing filament. The trigger is represented by a short section of RNA synthesized by primary enzyme, and each trigger is eventually replaced by DNA.
Instead, in the delayed filament each single fragment of Okazaki must be triggered and these triggers are converted into DNA before the ligase unites the fragments together.
The helix is ​​an enzyme that performs the double propeller at the level of the replication force, separating the two filaments.
The protein that binds single-stranded DNA aligns along stranded DNA filaments, keeping them separate, while they work as molds for the synthesis of new complementary filaments.

filamento dna
Enzymes that control and correct errors in DNA replication
Errors in initial wrap between new nucleotides and mold filaments are quite frequent.
Polymerase itself checks for errors during replication, when it finds an improperly padded nucleotide, removes and resumes synthesis.
For repairing improper use of polymers, the cells use special enzymes that recognize and correct inappropriate paired nucleotides.
Nuclease is the enzyme that removes the damaged portion, then replaced by other nucleotides, thanks to the polymerase and the ligase, in a process called nucleotide excision repair.
Hereditary xeroderma pigmentous disease is caused by a deficiency of an enzyme involved in excision repair, and causes hypersensitivity to light and skin cancers.
In principle, most of the repair processes involve DNA molecule polymerase activity.
Normal DNA replication does not allow to complete the 5 'end, and therefore repeated replication cycles would lead to the production of ever-shorter DNA molecules.
Telomers are special nucleotide sequences, TTAGGGG, which do not contain genes.
Telomeric DNA protects the genes of the organism from erosion and prevents the extremities from activating cellular systems to monitor DNA damage.
Telomerase is a particular enzyme that allows to restore shortened telomers, catalyzing their elongation, thanks to an RNA molecule that acts as a mold for the new segments of the telomer at the 3 'end.
Telomerase is not present in most pluricellular cells, and therefore in somatic cells DNA tends to be shorter in elderly cells.
Thus, telomeres are likely to be the cause of the life-span of organisms.
Telomerase is present in the germ cells that give origin to the pegs and is therefore present in the infants.
Unfortunately telomerase keeps cancer cells alive by not shortening the telomeres.

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