Researchers at the University
of Illinois have discovered deoxyribozymes capable of cleaving
single-stranded DNA. The discovery of these molecules—also called catalytic
DNA—is expected to enable researchers to manipulate DNA more efficiently.
According to the researchers, deoxyribozymes cleave single-stranded DNA with
selectivity for sequence and site, which makes it a practical catalyst.
“Our work suggests that deoxyribozymes have significant potential as sequence-specific DNA cleavage reagents,” said Scott Silverman, chemistry professor at the University of Illinois. “By appropriately picking the recognition and enzyme regions of the catalyst, we should be able to cut many more DNA sequences than is possible with current restriction enzymes.” Restriction enzymes enable scientists to cut and paste sections of double-stranded DNA.
The new deoxyribozymes function in a way similar to that of restriction enzymes, but are able to cleave only single-stranded DNA. Silverman’s team will address this problem. “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,” said Silverman.
While they can cut double-stranded DNA, restriction enzymes inhibit researchers because each enzyme can only cut a limited number of DNA sequences. According to Silverman, commercially available restriction enzymes cut very few DNA sequences.
Deoxyribozymes require manganese and zinc ions in order to carry out catalytic reactions. Silverman says the necessity of the ions is intriguing. “Many natural protein-based nucleases similarly require two metal ions,” said Silverman. “One or both of the metals are presumably involved in the chemical mechanism by which our DNA catalyst achieves hydrolysis of the DNA backbone.”
The discovery was published in Nature Chemical Biology. Funding was provided by the National Institutes of Health, the Defense Threat Reduction Agency, and the David and Lucile Packard Foundation.
