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 Water world
20.11.2017 | Washington University in St. Louis

nachricht Carefully crafted light pulses control neuron activity
20.11.2017 | University of Illinois at Urbana-Champaign

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

Im Focus: Wrinkles give heat a jolt in pillared graphene

Rice University researchers test 3-D carbon nanostructures' thermal transport abilities

Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

Water world

20.11.2017 | Life Sciences

Less is more to produce top-notch 2D materials

20.11.2017 | Materials Sciences

Carefully crafted light pulses control neuron activity

20.11.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>