A multi-function protein is key to stopping genomic parasites from 'jumping'

September 23, 2014

Most organisms, including humans, have parasitic DNA fragments called "jumping genes" that insert themselves into DNA molecules, disrupting genetic instructions in the process. And that phenomenon can result in age-related diseases such as cancer. But researchers at the University of Rochester now report that the "jumping genes" in mice become active as the mice age when a multi-function protein stops keeping them in check in order to take on another role.

In a study published today in Nature Communications, Professor of Biology Vera Gorbunova and Assistant Professor of Biology Andrei Seluanov explain that a protein called Sirt6 is needed to keep the —technically known as retrotransposons—inactive. That's an entirely different function from the ones scientists had long associated with Sirt6, such as the repairing of broken DNA molecules and regulating metabolism.

"About half of the human genome is made up of retrotransposons," said Gorbunova. "By better understanding why these genomic parasites become active, we hope to better understand and perhaps delay the aging process in humans."

For the most part, retrotransposons remain silent and inactive in organisms' genomes. But once they do become active, these DNA fragments can duplicate themselves and "jump" to new areas of the genome, disrupting the function of another gene by landing in an important part of the gene and changing its DNA sequence information.

But what happens to the Sirt6 proteins that kept the jumping genes inactive in younger ? The answer lies in the role that Sirt6 plays in repairing DNA damage. Cells accumulate a lot of DNA damage over time that needs to be constantly repaired. As cells get older, Sirt6 becomes busier in taking care of the DNA damage. Gorbunova and Seluanov hypothesized that Sirt6 becomes so preoccupied in repairing DNA damage in older cells that it is no longer available to keep the jumping genes inactive.

To test the theory, the team artificially caused DNA damage in young cells using gamma radiation or the chemical hydrogen peroxide. Once the damage took place, Sirt6 was immediately recruited to the damaged sites of the DNA to do its repair work. Gorbunova and Seluanov found that the stressed cells—the ones with increased DNA damage—had a higher rate of "jumping gene" activity, when compared to the other cells. Then, when the amount of Sirt6 was artificially increased in the stressed cells, the retrotransposons did not become as readily active, keeping the genome safe.

"This suggests that supplying more Sirt6 protein might protect older cells from aging," said Gorbunova. "The idea would be to increase the Sirt6 pool so that enough proteins are available for both DNA repair and for keeping the inactive."

Explore further: Scientists identify protein that improves DNA repair under stress

Related Stories

Scientists identify protein that improves DNA repair under stress

June 16, 2011
Cells in the human body are constantly being exposed to stress from environmental chemicals or errors in routine cellular processes. While stress can cause damage, it can also provide the stimulus for undoing the damage. ...

Less effective DNA repair process takes over as mice age

September 9, 2014
As we and other vertebrates age, our DNA accumulates mutations and becomes rearranged, which may result in a variety of age-related illnesses, including cancers. Biologists Vera Gorbunova and Andei Seluanov have now discovered ...

Strict genomic partitioning by biological clock separates key metabolic functions

July 31, 2014
Much of the liver's metabolic function is governed by circadian rhythms – our own body clock – and UC Irvine researchers have now found two independent mechanisms by which this occurs.

Scientists identify 'long distance scanner' for DNA damage

February 19, 2014
Scientists at the University of Bristol have discovered that a mechanism for preventing mutation within important genes involves long distance scanning of DNA by a molecular motor protein.

Recommended for you

Exploring disease predisposition to deliver personalized medicine

October 23, 2017
Geneticists from the University of Geneva have taken an important step towards true predictive medicine. Exploring the links between diseases and tissue-specific gene activity, they have been able to build a model that constitutes ...

Maternal diet may program child for disease risk, but better nutrition later can change that

October 20, 2017
Research has shown that a mother's diet during pregnancy, particularly one that is high-fat, may program her baby for future risk of certain diseases such as diabetes. A new study from nutrition researchers at the University ...

New gene editing approach for alpha-1 antitrypsin deficiency shows promise

October 20, 2017
A new study by scientists at UMass Medical School shows that using a technique called "nuclease-free" gene editing to correct cells with the mutation that causes a rare liver disease leads to repopulation of the diseased ...

Researchers find evidence of DNA damage in veterans with Gulf War illness

October 19, 2017
Researchers say they have found the "first direct biological evidence" of damage in veterans with Gulf War illness to DNA within cellular structures that produce energy in the body.

Researchers drill down into gene behind frontotemporal lobar degeneration

October 19, 2017
Seven years ago, Penn Medicine researchers showed that mutations in the TMEM106B gene significantly increased a person's risk of frontotemporal lobar degeneration (FTLD), the second most common cause of dementia in those ...

Genetic variants associated with obsessive-compulsive disorder identified

October 18, 2017
(Medical Xpress)—An international team of researchers has found evidence of four genes that can be linked to obsessive-compulsive disorder (OCD). In their paper published in the journal Nature Communications, the group ...

0 comments

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.