Proteins that work at the ends of DNA could provide cancer insight
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 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.
More information: The paper, "POT1-TPP1 Regulates Telomeric Overhang Structural Dynamics'" is available online: www.sciencedirect.… 212612003000
Journal reference: Structure
Provided by University of Illinois at Urbana-Champaign
- Study identifies a key molecular switch for telomere extension by telomerase Nov 23, 2011 | not rated yet | 0
- It takes two to tangle: Scientists further unravel telomere biology Nov 21, 2012 | not rated yet | 0
- Study explores possible 'safe and effective' anti-cancer therapy Feb 03, 2012 | not rated yet | 0
- Alternate ending -- living on without telomerase Nov 03, 2011 | not rated yet | 0
- Lab identifies elusive telomere RNA subunit in single cell model Dec 27, 2007 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013 As an experiment, for the past few months I've been consuming at least one portion of Jell-O or unflavored Knox gelatin per day. I'm 64, in very...
Alcohol and acetaminophen
May 13, 2013 Edit: sorry for the typo in the title , can't edit I looked around on google quite a bit and it's very hard to find precise information on the...
Marie Curie's leukemia
May 13, 2013 Does anyone know what might be the cause of Marie Curie's cancer
- More from Physics Forums - Medical Sciences
More news stories
Nearly 20 percent of kidneys that are recovered from deceased donors in the U.S. are refused for transplant due to factors ranging from scarring in small blood vessels of the kidney's filtering units to the organ going too ...
Medical research 50 minutes ago | not rated yet | 0 |
Discovery of circadian clock in mice hair reveals period of time when damage from radiotherapy can be quickly repaired
Discovering that mouse hair has a circadian clock - a 24-hour cycle of growth followed by restorative repair - researchers suspect that hair loss in humans from toxic cancer radiotherapy and chemotherapy ...
Medical research 1 hour ago | 5 / 5 (1) | 1 |
Salamanders' immune systems are key to their remarkable ability to regrow limbs, and could also underpin their ability to regenerate spinal cords, brain tissue and even parts of their hearts, scientists have ...
Medical research 2 hours ago | not rated yet | 0 |
New research from the University of Southampton has shown that blind and visually impaired people have the potential to use echolocation, similar to that used by bats and dolphins, to determine the location of an object.
Medical research 4 hours ago | not rated yet | 1 |
A novel vaccine study from South Dakota State University (SDSU) will headline the groundbreaking research that will be unveiled at the American Association of Pharmaceutical Scientists' (AAPS) National Biotechnology Conference ...
Medical research 5 hours ago | not rated yet | 0
(Medical Xpress)—Individuals who learn two languages at an early age seem to switch back and forth between separate "sound systems" for each language, according to new research conducted at the University of Arizona.
1 hour ago | 5 / 5 (2) | 0 |
A Saudi man who had contracted the coronavirus has died, raising the death toll in the kingdom from the SARS-like virus to 16, the health ministry announced on Monday on its Internet website.
50 minutes ago | not rated yet | 0
Little is known about the effect of physical education (PE) on child weight, but a new study from Cornell University finds that increasing the amount of time that elementary schoolchildren spent in gym class reduces the probability ...
1 hour ago | not rated yet | 0
Video games that pit players against human-looking characters may be more likely to provoke violent thoughts and words than games where monstrous creatures are the enemy, according to a new study by researchers ...
1 hour ago | not rated yet | 0
A new "telerehabilitation" approach lets physical therapists assess patients with low back pain (LBP) over the Internet, with good accuracy compared with face-to-face examinations, reports a study in the May 15 issue of Sp ...
1 hour ago | not rated yet | 0
New research suggests that a compound abundant in the Mediterranean diet takes away cancer cells' "superpower" to escape death. By altering a very specific step in gene regulation, this compound essentially re-educates cancer ...
1 hour ago | 5 / 5 (2) | 0 |