Featured Research

from universities, journals, and other organizations

Novel technique reveals dynamics of telomere DNA structure: Chromosome-capping telomeres are a potential target for anti-cancer drugs

Date:
January 17, 2013
Source:
University of California - Santa Cruz
Summary:
Biomedical researchers studying aging and cancer are intensely interested in telomeres, the protective caps on the ends of chromosomes. In a new study, scientists used a novel technique to reveal structural and mechanical properties of telomeres that could help guide the development of new anti-cancer drugs.

Researchers observed the unfolding of telomere G-quadruplex structures using a combination of single-molecule FRET and magnetic tweezers, as shown in this diagram. DNA structural transitions between the folded state (far left) and unfolded state (far right) were monitored in real-time as the efficiency of energy transfer between a FRET donor dye (green) and acceptor dye (red) attached to the DNA.
Credit: Artwork by Benjamin Akiyama

Biomedical researchers studying aging and cancer are intensely interested in telomeres, the protective caps on the ends of chromosomes. In a new study, scientists at UC Santa Cruz used a novel technique to reveal structural and mechanical properties of telomeres that could help guide the development of new anti-cancer drugs.

Telomeres are long, repetitive DNA sequences at the ends of chromosomes that serve a protective function analogous to that of the plastic tips on shoelaces. As cells divide, their telomeres get progressively shorter, until eventually the cells stop dividing. Telomeres can grow longer, however, through the action of an enzyme called telomerase, which is especially active in cells that need to keep dividing indefinitely, such as stem cells. Researchers have also found that most tumor cells show high telomerase activity.

Michael Stone, an assistant professor of chemistry and biochemistry at UC Santa Cruz, said his lab is particularly interested in the folding and unfolding of a DNA structure at the tail end of the telomere, known as a G-quadruplex, because it plays a key role in regulating telomerase activity.

"Most cancer cells use telomerase as one mechanism to maintain uncontrolled growth, so it is an important target for anti-cancer therapeutics," Stone said. "The G-quadruplex structures of telomere DNA inhibit the function of the telomerase enzyme, so we wanted to understand the mechanical stability of this structure."

Xi Long, a graduate student in Stone's lab, led the project, which involved integrating two techniques to manipulate and monitor single DNA molecules during the unfolding of the G-quadruplex structure. A "magnetic tweezers" system was used to stretch the DNA molecule, while a fluorescence microscopy technique was used to monitor small-scale structural changes in the DNA. The results, published in Nucleic Acids Research, showed that a relatively small structural displacement causes the G-quadruplex to unfold.

"Unlike other DNA structures, the G-quadruplex structure is fairly brittle. It takes very little perturbation to make the whole thing fall apart," Stone said. "We also found that the unfolded state has a highly compacted conformation, which tells us that it still has interactions that favor the folding reaction."

These findings have implications for understanding the molecular mechanisms of telomere-associated proteins and enzymes involved in the unfolding reaction, as well as for rational design of anti-cancer drugs, Stone said. Small molecules that bind to and stabilize telomere DNA G-quadruplexes have shown promise as anti-cancer drugs.

The integration of fluorescence measurements and magnetic tweezers is a powerful method for monitoring DNA structural dynamics, and as biophysical techniques go, it is not hard to implement, Stone said. His lab worked with DNA molecules containing the G-quadruplex sequence from human telomere DNA, attaching one end of the DNA to a glass slide and the other end to a tiny magnetic bead. A magnet held above the sample pulled on the bead, exerting a stretching force on the DNA molecule that varied according to how close the magnet was to the sample.

At the same time, the researchers used a fluorescence technique called single-molecule FRET (Fφrster resonance energy transfer) to monitor small-scale structural changes in the DNA. "FRET can be thought of as a molecular ruler," Stone said. As energy from one fluorescent dye molecule is transferred to a second dye molecule, the efficiency of the energy transfer can be measured in real time. The dye molecules can be coupled directly to the DNA molecule at specific sites, allowing researchers to monitor the molecular dynamics of the system as it is being manipulated by the magnetic tweezers.

"You don't have to be a specialist to use this technique, so it can be easily transferred to other labs and broadly employed in these kinds of studies," Stone said.


Story Source:

The above story is based on materials provided by University of California - Santa Cruz. Note: Materials may be edited for content and length.


Journal Reference:

  1. X. Long, J. W. Parks, C. R. Bagshaw, M. D. Stone. Mechanical unfolding of human telomere G-quadruplex DNA probed by integrated fluorescence and magnetic tweezers spectroscopy. Nucleic Acids Research, 2013; DOI: 10.1093/nar/gks1341

Cite This Page:

University of California - Santa Cruz. "Novel technique reveals dynamics of telomere DNA structure: Chromosome-capping telomeres are a potential target for anti-cancer drugs." ScienceDaily. ScienceDaily, 17 January 2013. <www.sciencedaily.com/releases/2013/01/130117133400.htm>.
University of California - Santa Cruz. (2013, January 17). Novel technique reveals dynamics of telomere DNA structure: Chromosome-capping telomeres are a potential target for anti-cancer drugs. ScienceDaily. Retrieved April 23, 2014 from www.sciencedaily.com/releases/2013/01/130117133400.htm
University of California - Santa Cruz. "Novel technique reveals dynamics of telomere DNA structure: Chromosome-capping telomeres are a potential target for anti-cancer drugs." ScienceDaily. www.sciencedaily.com/releases/2013/01/130117133400.htm (accessed April 23, 2014).

Share This



More Health & Medicine News

Wednesday, April 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Big Pharma Braces for M&A Wave

Big Pharma Braces for M&A Wave

Reuters - Business Video Online (Apr. 22, 2014) — Big pharma on the move as Novartis boss, Joe Jimenez, tells Reuters about plans to transform his company via an asset exchange with GSK, and Astra Zeneca shares surge on speculation that Pfizer is looking for a takeover. Joanna Partridge reports. Video provided by Reuters
Powered by NewsLook.com
How Smaller Plates And Cutlery Could Make You Feel Fuller

How Smaller Plates And Cutlery Could Make You Feel Fuller

Newsy (Apr. 22, 2014) — NBC's "Today" conducted an experiment to see if changing the size of plates and utensils affects the amount individuals eat. Video provided by Newsy
Powered by NewsLook.com
How to Master Motherhood With the Best Work/Life Balance

How to Master Motherhood With the Best Work/Life Balance

TheStreet (Apr. 22, 2014) — In the U.S., there are more than 11 million couples trying to conceive at any given time. From helping celebrity moms like Bethanny Frankel to ordinary soon-to-be-moms, TV personality and parenting expert, Rosie Pope, gives you the inside scoop on mastering motherhood. London-born entrepreneur Pope is the creative force behind Rosie Pope Maternity and MomPrep. She explains why being an entrepreneur offers the best life balance for her and tips for all types of moms. Video provided by TheStreet
Powered by NewsLook.com
Catching More Than Fish: Ugandan Town Crippled by AIDS

Catching More Than Fish: Ugandan Town Crippled by AIDS

AFP (Apr. 22, 2014) — The village of Kasensero on the shores of Lake Victoria was where HIV-AIDS was first discovered in Uganda. Its transient population of fishermen and sex workers means the nationwide programme to combat the virus has had little impact. Duration: 02:30 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins