Thursday, November 25, 2010

Canine Cauliflower Ear

ARSENIC AND DNA supercoiling. CARNIVAL OF THE

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Each of our cells contains about 2 meters of DNA
, all tucked inside the nucleus, which is a million times smaller. This requires a high state of structural organization of a molecule to pack so much in such a small space.
To make things even more complicated is the double helix structure of DNA, indefatigable in order for the cell to faithfully replicate the information it contains, the filaments that compose it must be separated and this requires the breaking of hydrogen bonds that provide structural stability. Before you understand how this can be done successfully we must speak of an important property of DNA known as supercoiling.
The term supercoiling another does not mean that wrapping something that is already wrapped. A classic example is that in these cases to make the meaning of the term applied to DNA supercoiling is the telephone wire.
As shown in the image on the right, a wire is wrapped with a spiral pattern similar to DNA and many of us have noticed that sometimes tends to become entangled in a strange way. This is due to a twist of the thread that causes it to coil back on itself, here is an example of supercoiling (shown in the end Supercoil). The comparison is guessed because basically, as we just said, the telephone cable has a structure similar to that of the DNA helix, and derives its was this observation that prompted one scientist, Jerome Vinograd and colleagues to explain some properties of small circular DNA . The DNA it forms from two complementary strands that wrap themselves up around an imaginary axis further folding or twisting of the structure results in supercoiling. As mentioned by you can see that the DNA molecule to be inserted into a small room as the core strength to present some form of supercoiling. The supercoiling is an important aspect of the tertiary structure of DNA. We see the fundamental properties of supercoiling and how it occurs. To fully understand what is the supercoiling of DNA, scientists have focused on small circular DNA such as plasmids or DNA viruses, in many cases, what determines the onset of DNA supercoiling a disalvvolggimento the same molecule, in other words, the DNA undergoes a structural change that causes a decrease in the number of turns of helix.

As shown in the side we see a fragment of circular DNA in the relaxed state that has 8 turns of helix, one for every 10.5 base pairs for a total of 84 base pairs. If any of these tours is removed in the DNA molecule is a structural deformation induced by 12 base pairs (b) for each revolution of propeller instead of the 10.5 structure B. It follows that this deformation makes the structure less stable. Normally, this deformation is redressed through the winding axis DNA upon itself to give a supercoiling (c). As shown in Figure (d) the disavvolgimento causes a separation of the two DNA strands.
cells remain in a partially disavvolto the DNA molecule, that in order to facilitate the process of compaction, also disalvoggimento is essential for many enzymes that participate in processes involving DNA and which have among their functions the separation of double helix, it was partially disavvolto can be maintained only if the DNA is in a closed form or if you move or stabilize the protein so that its complementary chains are not able to turn in on themselves. The
supercoiling but not a completely random process, is highly regulated and has an influence on cellular mechanisms involving DNA. In fact, in every cell there are enzymes that are responsible for wrapping and carrying out the double helix. The enzymes that are responsible for determining the increase or decrease disalvoggimento
are known as DNA topoisomerases.

We can distinguish three types of DNA topoisomerases.

The class of topoisomerase I: solve the problem of the tension that we have described before, caused dall'avvolgimento and the development of DNA. An example of how this happens is shown in the picture below from the PDB file 1a36 .

This enzyme wraps around the DNA and makes a cut in one of the filaments. Then, while still clinging to the point when freshly cut, the enzyme allows the propeller to turn, to carry out the windings in excess or defect. When the DNA is relaxed, topoisomerase reconnects broken filament, restoring the DNA double helix.
The DNA topoisomerase I in the class are of two types:

Topoisomerase IA:
introduce an incision in a polynucleotide and pass the second polynucleotide through the gap that has been formed. The two ends are then resolder. This mode of action changes the number of times a filamneto cross each other in a circular molecule.

Topoisomerase IB:
act in a manner similar to the type IA enzymes, although details of the mechanism are different.
Untangling DNA
The class of topoisomerase II: specialize in sorting out the DNA in the nucleus. They cut both strands of the double helix, thereby leading to the formation of a gap and leads through which is passed a second segment of the propeller. Eukaryotic topoisomerases constitute the majority of the nuclear matrix, similar to a national network scaffolding that runs throughout the nucleus and serve to maintain the structure of chromatin and to separate DNA molecules.
For example, when a cell is dividing, the copies of the chromosome must be separated.
In the process of separating certain regions of the two homologous chromosomes could tangle with each other, creating some real problems in the separation. The class of topoisomerase II solves this problem by allowing the DNA helix to pass through each other. Cut both strands of a DNA double helix, while maintaining a firm grip on both halves. Then, passes the other strand of DNA through the opening, resolving the tangle. Finally, sews together the terminals that had cut off, restoring the DNA. The DNA topoisomerase
themselves do not carry the double helix of DNA, but solve the problem so-called topological, counterbalancing the supercoiling that would be introduced in the DNA molecule at the time of passage of the hairpin replication. This allows the double helix of DNA to be open like a zipper co filaments literally drawn on opposite sides without the molecule rotates.
Toxins and Treatments.
It follows from the above that the process that causes relaxation of the double helix resulting in separation of the latter are crucial for the proper maintenance of DNA. So are ideal targets for topoisomerase poisons. If topoisomerases are blocked, the cell encounters a problem during the transcription of DNA during cell division. Cancer chemotherapy exploits this process, using drugs that block the topoisomerase to kill cancer cells that divide rapidly. For example, the anthracycline-containing drugs such as doxorubicin and daunorubicin, attack the class of topoisomerase II, and the plant toxin blocks the action campotecina relaxing class of topoisomerase I.
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