Newly found DNA catalysts cleave DNA with water molecule

August 16, 2009

Better tools for manipulating DNA in the laboratory may soon be possible with newly discovered deoxyribozymes (catalytic DNA) capable of cleaving single-stranded DNA, researchers at the University of Illinois say.

The deoxyribozymes accomplish the DNA with the sequence-selectivity and site-selectivity required for a practical catalyst, the researchers say.

"Our work suggests that deoxyribozymes have significant potential as sequence-specific DNA cleavage reagents," said chemistry professor Scott Silverman. "The hope is that we can take this fundamental advance and develop the ability to use DNA as a practical catalyst to cleave double-stranded DNA."

Silverman, postdoctoral research associate Madhavaiah Chandra and graduate student Amit Sachdeva report their discovery in a paper accepted for publication in Nature and posted on the journal's Web site.

The researchers discovered the new deoxyribozymes while searching for artificial sequences of DNA that could cleave proteins. The newly found catalysts function in a fashion similar to restriction enzymes, although to date by cleaving only single-stranded DNA.

Restriction enzymes, which allow scientists to cut and paste portions of double-stranded DNA, are the fundamental catalysts of .

Each restriction enzyme, however, has a limited number of DNA sequences it can cut. Consequently, only a few percent of arbitrarily chosen DNA sequences can be cut by commercially available restriction enzymes.

Like natural restriction enzymes, the new catalysts are both sequence-specific and site-specific. "This means we can target a particular sequence, and we know we will cut at only one site within that sequence," Silverman said. "By appropriately picking the recognition and enzyme regions of the catalyst, we should be able to cut many more than is possible with current restriction enzymes."

The new DNA catalysts require two - manganese and zinc - to carry out their catalysis, "which is intriguing, because many natural protein-based nucleases (which cleave DNA) similarly require two metal ions," Silverman said. "One or both of the metals are presumably involved in the chemical mechanism by which our DNA catalyst achieves hydrolysis of the DNA backbone."

DNA hydrolysis is a very challenging chemical reaction, much more difficult to perform than the cleavage of a strand of RNA, Silverman said. In cleaving DNA, a water molecule must be brought in for the breaking reaction to occur. Also, both the DNA and the must be arranged appropriately in three-dimensional space.

How all of this happens with the DNA catalysts is not yet clear. Silverman's research group continues to probe the structure and mechanism of the catalysts, along with identifying and characterizing catalysts with different recognition sites.

"So far, we have achieved cleavage of single-stranded DNA targets," Silverman said. "The next big step is to cleave double-stranded DNA targets."

Source: University of Illinois at Urbana-Champaign (news : web)

Explore further: Purdue researchers use enzyme to clip 'DNA wires'

Related Stories

Purdue researchers use enzyme to clip 'DNA wires'

March 1, 2005

Researchers at Purdue University have attached magnetic "nanoparticles" to DNA and then cut these "DNA wires" into pieces, offering the promise of creating low-cost, self-assembling devices for future computers. Findings ...

DNA constraints control structure of attached macromolecules

June 28, 2005

A new method for manipulating macromolecules has been developed by researchers at the University of Illinois at Urbana-Champaign. The technique uses double-stranded DNA to direct the behavior of other molecules. In previous ...

Recommended for you

'Hog-nosed rat' discovered in Indonesia

October 6, 2015

Museum of Natural Science Curator of Mammals Jake Esselstyn at Louisiana State University and his international collaborators have discovered a new genus and species on a remote, mountainous island in Indonesia. This new ...

Stress in adolescence prepares rats for future challenges

October 5, 2015

Rats exposed to frequent physical, social, and predatory stress during adolescence solved problems and foraged more efficiently under high-threat conditions in adulthood compared with rats that developed without stress, according ...

Most EU nations seek to bar GM crops

October 4, 2015

Nineteen of the 28 EU member states have applied to keep genetically modified crops out of all or part of their territory, the bloc's executive arm said Sunday, the deadline for opting out of new European legislation on GM ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.