Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

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

30.11.2012
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 DNA units that cap the ends of chromosomes. 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, cell biologists postulate that telomere length can determine the lifespan of a cell. Cancer cells, however, have a way to get around this limitation: An enzyme called telomerase 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 molecules 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 regulatory proteins 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 protein complex, 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-cancer drugs, 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 telomere-targeted drug screening,” Myong said.

The American Cancer Society and the Human Frontier Science Research Program supported this work.

Liz Ahlberg | EurekAlert!
Further information:
http://www.illinois.edu

More articles from Life Sciences:

nachricht Protein Shake-Up
27.03.2015 | Oak Ridge National Laboratory

nachricht How did the chicken cross the sea?
27.03.2015 | Michigan State University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Experiment Provides the Best Look Yet at 'Warm Dense Matter' at Cores of Giant Planets

In an experiment at the Department of Energy's SLAC National Accelerator Laboratory, scientists precisely measured the temperature and structure of aluminum as...

Im Focus: Energy-autonomous and wireless monitoring protects marine gearboxes

The IPH presents a solution at HANNOVER MESSE 2015 to make ship traffic more reliable while decreasing the maintenance costs at the same time. In cooperation with project partners, the research institute from Hannover, Germany, has developed a sensor system which continuously monitors the condition of the marine gearbox, thus preventing breakdowns. Special feature: the monitoring system works wirelessly and energy-autonomously. The required electrical power is generated where it is needed – directly at the sensor.

As well as cars need to be certified regularly (in Germany by the TÜV – Technical Inspection Association), ships need to be inspected – if the powertrain stops...

Im Focus: 3-D satellite, GPS earthquake maps isolate impacts in real time

Method produced by UI researcher could improve reaction time to deadly, expensive quakes

When an earthquake hits, the faster first responders can get to an impacted area, the more likely infrastructure--and lives--can be saved.

Im Focus: Atlantic Ocean overturning found to slow down already today

The Atlantic overturning is one of Earth’s most important heat transport systems, pumping warm water northwards and cold water southwards. Also known as the Gulf Stream system, it is responsible for the mild climate in northwestern Europe. 

Scientists now found evidence for a slowdown of the overturning – multiple lines of observation suggest that in recent decades, the current system has been...

Im Focus: Robot inspects concrete garage floors and bridge roadways for damage

Because they are regularly subjected to heavy vehicle traffic, emissions, moisture and salt, above- and underground parking garages, as well as bridges, frequently experience large areas of corrosion. Most inspection systems to date have only been capable of inspecting smaller surface areas.

From April 13 to April 17 at the Hannover Messe (hall 2, exhibit booth C16), engineers from the Fraunhofer Institute for Nondestructive Testing IZFP will be...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

World Conference On Regenerative Medicine 2015: Registration And Abstract Submission Now Open

25.03.2015 | Event News

University presidents from all over the world meet in Hamburg

19.03.2015 | Event News

10. CeBiTec Symposium zum Big Data-Problem

17.03.2015 | Event News

 
Latest News

Two Most Destructive Termite Species Forming Superswarms in South Florida

27.03.2015 | Agricultural and Forestry Science

ORNL-Led Team Demonstrates Desalination with Nanoporous Graphene Membrane

27.03.2015 | Materials Sciences

Coorong Fish Hedge Their Bets for Survival

27.03.2015 | Ecology, The Environment and Conservation

VideoLinks
B2B-VideoLinks
More VideoLinks >>>