Researchers from the Andalusian centre for Molecular Biology and regenerative Medicine (CABIMER) and from the University of Seville have taken a step forward with a study of something as essential for life as the molecules of DNA. They have studied the role of the protein PIF1, capable of undoing different structures in these molecules. These molecules contain the instructions that allow cells to function correctly, so that when there is an alteration that is not repaired properly, mutations can occurred that can cause problems for the health of the body.
To avoid these problems, it is necessary to keep the DNA molecule intact, so safeguarding the genetic material. However, the cell's own metabolism, and especially its own use of this information, means that there are habitual physical and chemical alterations that could compromise the information the DNA contains and cause mutations. In fact, a cell can suffer tens of mutations every day.
To, as much as possible, avoid any loss of genetic information, multiple mechanisms have evolved, and these are capable of fighting these alterations and repairing the DNA. If these mechanisms are not sufficiently efficient to repair all the alterations, mutations build up that are natural causes of cell ageing and, occasionally, can lead to the appearance of various pathologies, including cancer.
"Although much is known about the basic mechanisms of DNA repair that act when the molecule is in a state of normal configuration, still little is known about the additional factors require to repair the parts of the DNA that are configured atypically. In this article, published in Cell Reports, we have discovered that protein PIF1, a protein with the ability to undo various DNA structures, acts during the repair of DNA breaks which can form a cross-linked structure known as a G-quadruplex," explains the scientist and author or the study Pablo Huertas.
These structures are produced when there are areas in the structure of the DNA that are rich in guanine, one of the four "letters" of the genetic alphabet, which can interact with each other.
"Our data suggests that the presence of these structures impede the work of the repair machinery, unless they are undone by PIF1. For this to happen, PIF1 needs to interact with the protein BRCA1, known for its importance in this process and whose mutations cause breast cancer," adds Huertas.
Identifying this new factor, which is associated with the repair of DNA breaks, can, in the long term, bring about a better understanding of the processes that cause the accumulation of mutations associated with the appearance of tumours. In addition, better understanding what is happening could open new therapeutic options.
Some drugs that stabilise the G-quadruplex are included in clinical studies for fighting cancer, so knowing what factors are going to interact with these DNA structures will allow doctors to better choose what type of patients would best benefit from these treatments.
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