Will targeted gene demethylation help in cancer treatment?
A new mechanism for "turning on" genes will help in the fight against cancer
NanoNewsNet based on the materials of Fox Chase Cancer Center:
Fox Chase Researchers Identify New Mechanism Used by Cells to Reverse Silenced Genes
Scientists from the Cancer Center in Fox Chase, Philadelphia, USA, have discovered a new mechanism used by cells to "turn on" silent genes. This process is essential for preventing the development of cancer and can be used to develop new treatments specifically focused on the changes underlying this disease. An article about the study (Thymine DNA Glycosylase Is Essential for Active DNA Demethylation by Linked Deamination-Base Excision Repair) is published in the journal Cell.
Alfonso Bellacosa, associate Professor at Fox Chase, and his colleagues are studying one of the main epigenetic mechanisms for suppressing gene activity - DNA methylation. The essence of DNA methylation is that in order to "turn off" a gene, the cell "puts" a chemical label on it, or more precisely, binds a small molecule to it – a methyl group; without a methyl group, the gene remains active.
The process of DNA methylation is of great interest to scientists, as it is part of normal gene regulation. But if methylation turns off the genes that normally inhibit the development of cancer, tumor formation becomes possible. Therefore, the mechanism of action of some anticancer drugs is based on demethylation, that is, the removal of methyl groups associated with DNA. But such drugs demethylate DNA non-specifically, causing side effects and other problems.
Scientists have been studying how cells add methyl groups to genes for many years, but the idea of how the process of their demethylation proceeds remains less clear. In particular, some researchers have suggested that demethylation occurs only passively. An example of such passive demethylation of DNA is the process of its replication, when DNA with a methyl group added to it creates its copy without methyl.
Dr. Bellacose and his colleagues managed to present the first direct evidence that DNA demethylation is an active process controlled by a specific protein. Scientists have established that the thymine DNA glycosylase (TDG) protein, known for its participation in DNA repair, is responsible for the removal of methyl groups. Experiments on mice with no TDG activity have shown that this protein is necessary for survival. After studying the dead mouse embryos in detail, they found that methylation was grossly violated in them – genes that normally should be demethylated remained silent.
"In order to demethylate DNA, thymine-DNA-glycosylase needs a second protein, so future therapies may target this mechanism to, for example, include specific anti–cancer genes," says Dr. Bellacosa. "Since we now know that there are proteins that actively affect demethylation, we can imagine a new type of anti-cancer therapy that allows demethylation of specific genes. Such therapy would be more precise and more targeted."
In addition to cancer treatment, this knowledge can be applied to other diseases, which are also characterized by violations in the methylation process. However, Professor Bellacosa warns that scientists do not yet know how to direct the effect of drugs on specific genes, so any practical benefit from this discovery can be extracted only in the future.
"This is a purely fundamental study aimed at deciphering the process of switching genes on and off," he says. "It will be possible to take full advantage of this new knowledge only in a few years. But we will achieve this."
Portal "Eternal youth" http://vechnayamolodost.ru05.07.2011