Newly found enzymes may play early role in cancer

December 24, 2008

Researchers have discovered two enzymes that, when combined, could be involved in the earliest stages of cancer. Manipulating these enzymes genetically might lead to targeted therapies aimed at slowing or preventing the onset of tumors.

"We could conceivably reactivate a completely normal gene in a tumor cell - a gene that could prevent the growth of a tumor if reactivated," says David Jones, Ph.D., professor of oncological sciences at the University of Utah and senior director of early translational research at the university's Huntsman Cancer Institute (HCI).

"We believe this could be one of the earliest processes to go wrong in cancer," he adds. "By manipulating these enzymes, we could possibly prevent or slow the onset of tumors."

The enzymes appear to control an "on-and-off switch" for critical genes that could trigger cancer or numerous other diseases and birth defects. The research is published in the December 26 issue of Cell.

Using zebrafish that share similar genetics to humans, the HCI scientists identified a previously unknown enzyme process that controls the levels of DNA methylation on genes.

"Methylation is a cellular process that is required for healthy cell growth and development, but it can go awry in cancer and diseased cells," says Brad Cairns, Ph.D., HCI investigator and professor of oncological sciences at the University of Utah. "You can think of DNA methylation as an on-and-off switch. Methylation silences or 'shuts off' genes that need to be turned off or are not functioning as they should, whereas the reverse process called demethylation 'turns on' healthy genes and genes needed at critical times in development," he says.

In cancer, this methylation process goes haywire, leading to tumor growth. Genes that should be "turned on" are not and vice versa.

The significance of this research is the discovery of two enzymes involved in DNA demethylation. Defects in DNA methylation balance are strongly associated with the early development of cancer, other diseases and birth defects, and the scientists say their study is the first clear evidence that this enzyme system plays a critical role in maintaining this balance. They also believe it's a process that can be reversed.

Further research will reveal if DNA methylation levels can be manipulated genetically. If so, it could lead to drugs to reactivate particular genes and suppress tumor growth. Remarkably, this system also helps protect the genome from mutations.

"We discovered a pair of enzymes that can remove methylated DNA, but if these enzymes work improperly, they will instead enhance the rate of mutations in methylated DNA and cause cancer progression," says Jones. "The question now is, when they work improperly, can we find ways to shut them off and prevent these mutations?"

The enzymes leading to DNA demethylation involve the coupling of a 5-meC deaminase enzyme, a G:T glycosylase enzyme and Gadd45, which is not an enzyme.

Source: University of Utah

Explore further: Scientists discover new system for human genome editing

Related Stories

Scientists discover new system for human genome editing

September 25, 2015

A team including the scientist who first harnessed the revolutionary CRISPR-Cas9 system for mammalian genome editing has now identified a different CRISPR system with the potential for even simpler and more precise genome ...

Scientists create rice variety with high folate stability

September 22, 2015

Researchers from Ghent University succeeded in stabilizing folates in biofortified rice in order to prevent their degradation upon long term storage. They used two strategies: by linking folates with folate binding proteins ...

Student tackles labeling RNA without genetic modification

September 21, 2015

Overcoming limitations of super-resolution microscopy to optimize imaging of RNA in living cells is a key motivation for physics graduate student Takuma Inoue, who works in the lab of MIT assistant professor of physics Ibrahim ...

MicroRNAs are digested, not absorbed

September 8, 2015

There has been a lot of controversy in recent years over the issue of whether exogenous microRNA molecules can be absorbed from food and even have a physiological effect. A new study by ETH professor Markus Stoffel using ...

Making nanowires from protein and DNA

September 3, 2015

The ability to custom design biological materials such as protein and DNA opens up technological possibilities that were unimaginable just a few decades ago. For example, synthetic structures made of DNA could one day be ...

Recommended for you

How the finch changes its tune

August 3, 2015

Like top musicians, songbirds train from a young age to weed out errors and trim variability from their songs, ultimately becoming consistent and reliable performers. But as with human musicians, even the best are not machines. ...

Machine Translates Thoughts into Speech in Real Time

December 21, 2009

( -- By implanting an electrode into the brain of a person with locked-in syndrome, scientists have demonstrated how to wirelessly transmit neural signals to a speech synthesizer. The "thought-to-speech" process ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.