OVER 60 YEARS AGO, James Watson
and Francis Crick
they described the DNA with its now iconic double helix. Today in Nature a group of Italian scientists, we describe a new code of Dna that reminds you of the corolla of a flower with the basic structure of DNA cruciform. Not only that: thanks to an approach analysts and mathematical, these scientists, directed by Marco Foiani
at the at the IFOM research center for the study of the formation of the development of tumors at the molecular level) and at the University of Milan have also understood that the protein allarmina protects this configuration of the Dna from the mechanical stress during dna replication. Stress that could damage chromosomes and lead to the onset of cancer. It is a discovery that may help clarify the molecular basis of the processes of repair and duplication of DNA and the mechanism of protection from cancer. The results, achieved thanks to the support of Foundation Airc
, open the way for the development of care anticancer complementary to the existing ones, to increase the effectiveness and reduce the toxicity. The ‘twists’ of the double helix In the cells the long sequence double-helix is compacted and wrapped in a complex of DNA, RNA and proteins called chromatin. To understand the way in which the DNA twists and contorts, it is important to
to understand how you can intervene at the molecular level to prevent or treat various diseases and in particular cancer. At the time of replication, the DNA of the mother cell, is wound on itself countless times, it splits in two so that the two daughter cells inherit the entire genetic make-up, and to be able to do so, it needs to be stretched and then rewound. In this phase, the double helix is subjected to so many twists that result in changes of shape and opening of the propeller itself. The mechanical stress on the Dna and the predisposition to cancer But why should you care this mechanism? The fact is that these stress, torsion and mechanical can damage chromosomes, and cause the loss of genetic material, predisposing to the onset of cancer. “Thanks to the application of sophisticated mathematical models we have identified a code that coordinates a number of cellular processes critical during replication of the chromosomes,” says Marco Foiani
, for years specialized in the processes of DNA repair. “The importance of the kinks in the DNA and therefore the mechanical stress, the DNA undergoes during the twists physiological in the process of replicative – says Foiani – had already been seen in the past, but since the Nineties, attention has focused mainly on the sequencing of the human genome, in the belief that this would have been enough to identify therapeutic solutions against diseases such as cancer. The sequencing was essential, but now we have discovered that there are new and important levels of organization for DNA”. A corolla of petals that protects the genetic sequence “We have carried out our investigation on the genomic instability and the mechanical aspects of the DNA – adds Yathish Achar
, the first author of the article – and now we are able to reconstruct the form of the dynamically the DNA in this process.” Kinks that occur along the DNA to form a sort of corolla the petals of a flower, within which is secured the sequence of the genetic material. At the base of the petals, the DNA assumes a conformation of a cross, similar to the thorns. The protection of the allarmina But these structures cruciform can be attacked by damaging the genetic material. The cell protects via a protein-specific
called, not surprisingly, allarmina. “I discovered that the allarmina protects the structures cruciform at the end of the Eighties, reconstructs, Marco Emilio Bianchi
, head of Unit of chromatin Dynamics, IRCCS Ospedale San Raffaele and professor of the University Vita-Salute San Raffaele – when I was a young researcher. I continued studying this protein, and I have given the name allarmina, because it is also involved in the signaling of the malaise of the individual cells the rest of the body”. Foiani and White had shared the lab at the University of Milan over twenty years ago, “it Is nice to find now the allarmina in this research, identifying a specific role in a code before a new song,” concludes Foiani. Because the discovery may help to treat tumors, But the significance of this discovery goes beyond the mere knowledge of a code unpublished DNA, and opens new perspectives for the identification of pharmacological targets for complementary anticancer therapy. "To be able to identify the processes that safeguard the integrity of the genome and its organization – concludes Foiani – is a significant advancement of knowledge in cancer research at the molecular level, laying the groundwork for the identification of combinations of therapies are more and more targeted against cancer cells, without damaging the genomes of healthy cells". It is believed that the protein-DNA interactions represent a target, important for the identification of therapeutic strategies that aim to prevent the expansion of cancer cells.
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