Proteins that work at the ends of DNA could provide cancer insight

November 29, 2012, University of Illinois at Urbana-Champaign
Researchers from the University of Illinois -- professor Sua Myong, left, and graduate student Helen Hwang -- determined the action of proteins that regulate the caps on the ends of DNA strands, creating an assay that could be used to screen anti-cancer drugs. Credit: L. Brian Stauffer

(Medical Xpress)—New insights into a protein complex that regulates the very tips of chromosomes could improve methods of screening anti-cancer drugs.

Led by bioengineering professor Sua Myong, the research group's findings are published in the journal Structure.

Myong's group focused on understanding the proteins that protect and regulate telomeres, segments of repeating units that cap the ends of . Telomeres protect the important gene-coding sections of DNA from loss or damage, the genetic equivalent of aglets – the covering at the tips of shoelaces that keep the ends of the laces from unraveling or fraying.

Telomeres play an important role in cell aging and death, since each time a cell divides, a little bit is lost from the end of the telomere. Thus, postulate that telomere length can determine the of a cell. , however, have a way to get around this limitation: An enzyme called that adds length to telomeres is highly active in cancer cells. This allows cancer cells to divide in perpetuity, running amok through tissues and systems.

"Cancer researchers want to get a hold of this problem, control this indefinite lengthening of the telomeres," said Myong, who also is affiliated with the Institute for Genomic Biology at the U. of I. "A lot of the anti-cancer drugs are targeted directly to these telomeres so that they can inhibit telomerase activity. The proteins we study regulate the activity of telomerase."

Using a technique developed at Illinois that allows researchers to watch single interact in real time, Myong's group determined how two proteins called POT-1 and TTP-1 bind to the telomere. POT-1 protects the fragile telomere ends from being attacked by other that might mistake the end for a broken or damaged area of DNA. When POT-1 and TTP-1 work together in a complex, they promote telomerase activity, an interesting target for cancer researchers.

The group found that on its own, POT-1 binds to the folded-up telomere in distinct steps at particular points in the telomere's DNA sequence, unfolding the telomere in a stepwise manner. However, the POT-1/TTP-1 complex surprised the researchers by binding, then freely sliding back and forth along the telomere end.

"Instead of stepwise binding, what we saw was a mobile , a dynamic sliding motion," Myong said. "Somehow it was as if the static binding activity of POT-1 is completely lost – the protein complex just slid back and forth. We were able to reproduce the data and confirm it with many different tail lengths of the telomeric DNA and we know now that the contact between POT-1 and the telomere is somehow altered when the partner protein comes and binds."

Next, the researchers will add telomerase and see how the sliding activity of the POT-1/TTP-1 complex affects telomerase activity. Myong postulates that the sliding may promote telomerase activity – and thus telomere lengthening – by making the end of the telomere accessible for the telomerase enzyme to bind.

"We are excited about the possibility that this kind of mobility can increase the telomerase extension activity," Myong said. "It's somehow engaging the enzyme so that it can stay bound to the DNA longer. So it must involve a direct interaction."

Ultimately, understanding the POT-1/TTP-1 complex gives drug developers a new target for anti-, and the assay Myong's group used to monitor the complex could offer a venue for evaluating telomere-targeting drugs.

"We want to extend our a basic science knowledge in telomere biology into causes of cancer and we hope that our assay can be useful for -targeted drug screening," Myong said.

Explore further: Study explores possible 'safe and effective' anti-cancer therapy

More information: The paper, "POT1-TPP1 Regulates Telomeric Overhang Structural Dynamics'" is available online: www.sciencedirect.com/science/ … ii/S0969212612003000

Related Stories

Study explores possible 'safe and effective' anti-cancer therapy

February 3, 2012
(Medical Xpress) -- New findings discovered by an international research team, which includes a professor from Western University, may lead to a safe and effective anti-cancer therapy.    A report published online ...

Alternate ending -- living on without telomerase

November 3, 2011
Scientists of the German Cancer Research Center have discovered an alternative mechanism for the extension of the telomere repeat sequence by DNA repair enzymes.

Recommended for you

Researchers devise decoy molecule to block pain where it starts

January 16, 2018
For anyone who has accidentally injured themselves, Dr. Zachary Campbell not only sympathizes, he's developing new ways to blunt pain.

Scientists unleash power of genetic data to identify disease risk

January 16, 2018
Massive banks of genetic information are being harnessed to shed new light on modifiable health risks that underlie common diseases.

Blood-vessel-on-a-chip provides insight into new anti-inflammatory drug candidate

January 15, 2018
One of the most important and fraught processes in the human body is inflammation. Inflammatory responses to injury or disease are crucial for recruiting the immune system to help the body heal, but inflammation can also ...

Molecule produced by fat cells reduces obesity and diabetes in mice

January 15, 2018
UC San Francisco researchers have discovered a new biological pathway in fat cells that could explain why some people with obesity are at high risk for metabolic diseases such as type 2 diabetes. The new findings—demonstrated ...

Obese fat becomes inflamed and scarred, which may make weight loss harder

January 12, 2018
The fat of obese people becomes distressed, scarred and inflamed, which can make weight loss more difficult, research at the University of Exeter has found.

Optimized human peptide found to be an effective antibacterial agent

January 11, 2018
A team of researchers in the Netherlands has developed an effective antibacterial ointment based on an optimized human peptide. In their paper published in the journal Science Translational Medicine, the group describes developing ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

Egleton
1 / 5 (1) Nov 30, 2012
Anti-cancer is good. What about using telemerase to repair ageing cell and prolong life?

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.