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Fox Chase researchers identify new mechanism used by cells to reverse silenced genes
Date:6/30/2011

PHILADELPHIA (June 30, 2011)Scientists at Fox Chase Cancer Center have discovered a new mechanism used by cells in the body to turn on silenced genes. This process is critical in preventing the development of cancersuggesting the possibility of new therapies that might target the specific changes underlying the disease. The findings will be published online in the journal Cell on June 30, 2011.

The process investigated by Alfonso Bellacosa, M.D., Ph.D., Associate Professor at Fox Chase, and his colleagues, is called methylation, in which the cell chemically tags genes to turn them off. More specifically, the cell silences a gene by adding a chemical compound known as a methyl group; without that methyl group, the gene remains active.

It's a process of great interest to scientists, Bellacosa explains, because methylation is a key part of normal gene regulation but, when it silences the genes that normally suppress tumors, it results in cancer. Indeed, some cancer drugs work by demethylatingmeaning, removing methyl groups from DNA. But those drugs will demethylate DNA non-specifically, he says, causing side effects and other problems.

Scientists have been investigating for years how the cell adds methyl groups to genes to turn them off, but have been less clear about the process of demethylation. For instance, some have suspected that demethylation only occurs passively, such as when DNA with an attached methyl group replicates, creating new DNA without a methyl group.

Now, Bellacosa and his team present the first direct evidence that demethylation can be, in fact, an active process, controlled by a specific protein along with clues about how to act on it in a targeted way.

The researchers found that one protein called thymine DNA glycosylase or TDGknown to help repair DNAis also responsible for removing methyl groups from DNA. Studies with mice that lacked TDG activity indicated the gene was needed for s
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Contact: Diana Quattrone
Diana.Quattrone@fccc.edu
215-728-7784
Fox Chase Cancer Center
Source:Eurekalert

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