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
How can there be villous adenoma in colon, if there are no villi there
15 hours ago As title suggest. Thanks :smile:
How can there be a term called "intestinal metaplasia" of stomach
May 21, 2013 Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
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...
- More from Physics Forums - Medical Sciences
More news stories
Every day, their baby stopped breathing, his collapsed bronchus blocking the crucial flow of air to his lungs. April and Bryan Gionfriddo watched helplessly, just praying that somehow the dire predictions ...
Medical research 6 hours ago | 5 / 5 (1) | 0
The human gut is loaded with commensal bacteria – "good" microbes that, among other functions, help the body digest food. The gastrointestinal tract contains literally trillions of such cells, and yet the ...
Medical research 10 hours ago | 5 / 5 (2) | 0 |
Swiss scientists reveal the mechanism responsible for aging hidden deep within mitochondria—and dramatically slow it down in worms by administering antibiotics to the young.
Medical research 10 hours ago | 4.8 / 5 (5) | 0 |
On May 22, JoVE will publish details of a technique to measure the health of human genetic material in relation to a patient's age. The method is demonstrated by the laboratory of Dr. Gil Atzmon at New York's Albert Einste ...
Medical research 13 hours ago | not rated yet | 0
(Medical Xpress)—Scientists supported by the National Institutes of Health have a new theory as to why a woman's fertility declines after her mid-30s. They also suggest an approach that might help slow ...
Medical research 15 hours ago | not rated yet | 0 |
Researchers from Queen Mary, University of London have led the largest sequencing study of human disease to date, investigating the genetic basis of six autoimmune diseases.
10 hours ago | 4 / 5 (1) | 0 |
Until now, little was scientifically known about the human potential to cultivate compassion—the emotional state of caring for people who are suffering in a way that motivates altruistic behavior.
7 hours ago | 5 / 5 (2) | 2 |
6 hours ago | 5 / 5 (1) | 0 |
A new approach for immunizing against influenza elicited a more potent immune response and broader protection than the currently licensed seasonal influenza vaccines when tested in mice and ferrets. The vaccine ...
7 hours ago | not rated yet | 0 |
In a series of lab experiments designed to unravel the workings of a key enzyme widely considered a possible trigger of rheumatoid arthritis, researchers at Johns Hopkins have found that in the most severe ...
9 hours ago | 5 / 5 (1) | 0 |
Researchers have developed a new drug delivery system that allows inhalation of chemotherapeutic drugs to help treat lung cancer, and in laboratory and animal tests it appears to reduce the systemic damage ...
9 hours ago | not rated yet | 0 |