Featured Research

from universities, journals, and other organizations

New Way To Lock DNA-slicing Enzyme Onto Chromosomes Could Lead To Novel Anti-cancer Drugs

Date:
December 15, 2003
Source:
St. Jude Children's Research Hospital
Summary:
Investigators at St. Jude Children's Research Hospital have discovered a new way that an enzyme crucial to the cell's ability to decode genes and duplicate chromosomes can be turned into a poison inside cancer cells.

Investigators at St. Jude Children's Research Hospital have discovered a new way that an enzyme crucial to the cell's ability to decode genes and duplicate chromosomes can be turned into a poison inside cancer cells.

The discovery is an important step toward designing a new class of anti-cancer drugs. Such drugs might be given with an existing agent that also targets this enzyme, creating a one-two punch against both solid tumors and leukemia, according to the researchers.

The enzyme, called Topoisomerase 1 (Top 1), is crucial to the cell's ability to unwind the DNA of chromosomes and separate the two strands making up a giant molecule. This activity permits the cell to transcribe (decode) specific genes or to make a copy of the entire chromosome. Duplication of chromosomes is critical to the process called mitosis, or cell division. After the cell divides, each daughter cell receives a copy of the entire set of duplicated chromosomes.

"We showed that modifying Top 1 so it became locked onto the DNA molecule is enough to cause cell death," said Mary-Ann Bjornsti, Ph.D., associate member of the St. Jude Molecular Pharmacology department. Bjornsti is the senior author of a report on this work, published in the November 25 issue of Proceedings of the National Academy of Sciences.

In order to begin unraveling the double-stranded DNA molecule, Top 1 first clamps onto the spiraled DNA molecule like a pair of C-shaped pliers grasping a twisted cable. Top 1 then breaks a chemical bond between two adjacent building blocks of one DNA strand and uses that bond to bind itself to one of the cut ends of that strand. This process allows the DNA next to Top 1 to rotate and reduce some of the tension in that part of the twisted molecule. This in turn paves the way for other enzymes to unravel the DNA and either decode a specific gene or duplicate the entire chromosome. Normally, Top 1 moves along the DNA, clipping the strand as it goes, while the other enzymes follow behind, unraveling the DNA. If the enzyme machinery following Top 1 is decoding a gene, only that part of the chromosome must be unraveled. If the machinery is duplicating the chromosome, the process of unraveling must continue along the entire molecule.

St. Jude investigators modified the top and bottom ends of the C-shaped enzyme so that the tips of the open ends of the enzyme were pulled together and locked Top 1 into place around the DNA. The Top 1 then acted as a roadblock to the enzyme machinery behind it.

"We found that Top 1 didn't even have to cut the DNA once it locked down on it in order to set off cell death," Bjornsti said. "Just being a roadblock to the enzyme machinery moving along the DNA behind it was enough to kill the cell."

This differs from the way a currently used anti-cancer drug, camptothecin (CPT), works. CPT works only during the part of the cell's life cycle called S phase, when the cell synthesizes duplicate chromosomes.

Because the new strategy can work whether the cell is in S phase or just decoding a single gene, a drug based on this approach could be particularly versatile.

"What's particularly exciting about our finding is that it is a proof-of-principle for a new class of anti-cancer drugs that can work in combination with CPT, a drug that has already shown itself to be a valuable cancer treatment," Bjornsti said. "By targeting Top 1 a different way, it might be possible to lessen the ability of cancer cells to become resistant to treatment, as they might when treated with CPT alone."

The use of CPT in pediatric cancer was also pioneered at St. Jude. Other authors of the study include Michael Woo and Hong Guo (St. Jude), and Carmen Losasso, Luca Pattarello and Piero Benedetti (University of Padua, Italy).

###

This work was supported in part by the National Institutes of Health, Ministero dell'Instruzione, dell'Universitΰ e della Ricerca Confinanziamento, Associazione Italiana per la Ricerca Sul Cancro, and ALSAC.

St. Jude Children's Research Hospital

St. Jude Children's Research Hospital is internationally recognized for its pioneering work in finding cures and saving children with cancer and other catastrophic diseases. Founded by late entertainer Danny Thomas and based in Memphis, Tennessee, St. Jude freely shares its discoveries with scientific and medical communities around the world. No family ever pays for treatments not covered by insurance, and families without insurance are never asked to pay. St. Jude is financially supported by ALSAC, its fundraising organization. For more information, please visit http://www.stjude.org.


Story Source:

The above story is based on materials provided by St. Jude Children's Research Hospital. Note: Materials may be edited for content and length.


Cite This Page:

St. Jude Children's Research Hospital. "New Way To Lock DNA-slicing Enzyme Onto Chromosomes Could Lead To Novel Anti-cancer Drugs." ScienceDaily. ScienceDaily, 15 December 2003. <www.sciencedaily.com/releases/2003/12/031215072523.htm>.
St. Jude Children's Research Hospital. (2003, December 15). New Way To Lock DNA-slicing Enzyme Onto Chromosomes Could Lead To Novel Anti-cancer Drugs. ScienceDaily. Retrieved July 23, 2014 from www.sciencedaily.com/releases/2003/12/031215072523.htm
St. Jude Children's Research Hospital. "New Way To Lock DNA-slicing Enzyme Onto Chromosomes Could Lead To Novel Anti-cancer Drugs." ScienceDaily. www.sciencedaily.com/releases/2003/12/031215072523.htm (accessed July 23, 2014).

Share This




More Health & Medicine News

Wednesday, July 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Courts Conflicted Over Healthcare Law

Courts Conflicted Over Healthcare Law

AP (July 22, 2014) — Two federal appeals courts issued conflicting rulings Tuesday on the legality of the federally-run healthcare exchange that operates in 36 states. (July 22) Video provided by AP
Powered by NewsLook.com
Why Do People Believe We Only Use 10 Percent Of Our Brains?

Why Do People Believe We Only Use 10 Percent Of Our Brains?

Newsy (July 22, 2014) — The new sci-fi thriller "Lucy" is making people question whether we really use all our brainpower. But, as scientists have insisted for years, we do. Video provided by Newsy
Powered by NewsLook.com
Scientists Find New Way To Make Human Platelets

Scientists Find New Way To Make Human Platelets

Newsy (July 22, 2014) — Boston scientists have discovered a new way to create fully functioning human platelets using a bioreactor and human stem cells. Video provided by Newsy
Powered by NewsLook.com
Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

TheStreet (July 21, 2014) — New research shows Gilead Science's drug Sovaldi helps in curing hepatitis C in those who suffer from HIV. In a medical study, the combination of Gilead's Hep C drug with anti-viral drug Ribavirin cured 76% of HIV-positive patients suffering from the most common hepatitis C strain. Hepatitis C and related complications have been a top cause of death in HIV-positive patients. Typical medication used to treat the disease, including interferon proteins, tended to react badly with HIV drugs. However, Sovaldi's %1,000-a-pill price tag could limit the number of patients able to access the treatment. TheStreet's Keris Lahiff reports from New York. Video provided by TheStreet
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