Navigation Links
Finding that 1-in-a-billion that could lead to disease
Date:8/19/2007

Errors in the genetic code can give rise to cancer and a host of other diseases, but finding these errors can be more difficult than looking for the proverbial needle in the haystack. Now, scientists at Johns Hopkins have uncovered how the tiny protein-machines in cells tasked to search for such potentially life-threatening genetic damage actually recognize DNA errors.

Appearing online next week in Nature, the Hopkins team describes how the UDG enzyme (for uracil DNA glycosylase) scrutinizes the shape of DNA building blocks by holding onto them and testing their fit into a specially sized pocket. The UDG pocket holds onto mistakes only the enzyme loses its grip on the right building blocks, which fall back in line with the rest of the DNA.

Locating damage in DNA is critical for a cells survival: So much can go wrong if damage goes unrepaired; cells cant tolerate any of this going on, says study author James Stivers, Ph.D., professor of pharmacology and molecular sciences at Hopkins. But the question is how these enzymes find the few mistakes among the billions of correct building blocks in DNA.

One typical error that occurs is to the DNA building block cytosine, being chemically converted to a similar-looking building block not normally found in DNA: uracil. Even water can cause DNA damage, says Stivers. Its not a fast reaction, but water does convert the occasional cytosine into an unwanted uracil.

To figure out how the enzyme responsible for cutting unwanted uracils out of DNA works, Stivers and colleagues studied a tiny segment of DNA. The research team then asked whether the breathing properties of DNA played a role in the search process of UDG. Although the bases in the DNA double helix resemble the rungs of a ladder, the rungs are not that sturdy, says Stivers. They actually pop in and out of the helix a bit, randomly.

Each time a base pops out of the helix, it exposes itself to water. Thus, using a special chemical trick, the team magnetically labeled water, which allowed them to follow the interaction of water with bases that had randomly popped out of the DNA helix. The researchers could then follow which bases pop out, and for how long, using a strong magnet.

After studying DNA breathing by itself, the researchers then added UDG into the mix. They saw that UDG holds onto the normal DNA building block thymine (T) after it pops out of the DNA on its own. However, because T is not identical to U, UDG then lets it fall back into DNA helix.

When the DNA contains an unwanted U, the UDG enzyme actually grabs on and pulls it all the way out and holds it in the enzymes pocket. Once sitting in this pocket, the enzyme clips out the U, leaving a gap in the DNA for other repair machinery to fill in with the correct building block.

This is the first time weve been able to actually see how an enzyme discriminates between right and wrong bases in DNA, says Stivers. Our discovery helps us appreciate what properties of DNA itself might lead to errors that are not repaired. The finding may help address how and where diseases like cancer arise in the genome.


'/>"/>

Contact: Audrey Huang
410-614-5105
Johns Hopkins Medical Institutions
Source:Eurekalert

Related biology news :

1. Finding Cures For Tropical Diseases: Is Open Source An Answer?
2. Fundamental Finding Yields Insight into Stem Cells, Cancer; Opens Door to Drug Discovery
3. Surprising findings reported about iron overload
4. Liposome finding implies electrical effect on cell development
5. Findings have implications for tracking disease, drugs at the molecular level
6. Finding hidden invaders in a Hawaiian rain forest
7. New Finding May Aid Adult Stem Cell Collection
8. Evolution of life on Earth may hold key to finding life in outer space
9. LIAI scientists make major finding on potential smallpox treatment
10. Study findings offer potential new targets for antibiotics
11. Finding rewrites the evolutionary history of the origin of potatoes
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/14/2017)... IBM ) is introducing several innovative partner startups at VivaTech ... startups and global businesses, taking place in Paris ... will showcase the solutions they have built with IBM Watson ... France is one of the most dynamic ... in the number of startups created between 2012 and 2015*, ...
(Date:5/16/2017)...   Bridge Patient Portal , an enterprise ... EMR Systems , an electronic medical record solutions ... established a partnership to build an interface between ... Centricity™ products, including Centricity Practice Solution (CPS), Centricity ... new integrations will allow healthcare delivery networks using ...
(Date:4/19/2017)... , April 19, 2017 ... its vendor landscape is marked by the presence of ... is however held by five major players - 3M ... these companies accounted for nearly 61% of the global ... leading companies in the global military biometrics market boast ...
Breaking Biology News(10 mins):
(Date:6/20/2017)... (PRWEB) , ... June 20, 2017 , ... ... announced that the CTNext board of directors has formed a Higher Education Entrepreneurship ... working group composed of institution presidents and other high-ranking representatives from 35 higher ...
(Date:6/20/2017)... ... June 20, 2017 , ... ... PhD, a well-versed leader with extensive assay development and biomarker expertise, as VP ... is a Boston CRO specializing in bio-analytical assay development and sample testing services. ...
(Date:6/19/2017)... ... 2017 , ... EDETEK, Inc., a clinical technology company focused ... two new additions of its award-winning cloud-based platform CONFORM™: Information Hub and Clinical ... Annual Meeting in Chicago, IL, June 19-22, 2017. , “Modern clinical trials use ...
(Date:6/16/2017)... ... June 16, 2017 , ... ... today announced that its Anzo Smart Data Lake® (Anzo SDL) solution was ... for the 2017 Software & Information Industry Association (SIIA) CODiE Awards. , ...
Breaking Biology Technology: