DNA BACKBONE SWAPS IN SULFUR - Chemical & Engineering

Oct 22, 2007 - ... of Shanghai Jiaotong University, in China, and biological chemist Peter C. Dedon and postdoc Shi Chen of MIT unearthed the modifica...
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NEWS OF THE W EEK

DNA BACKBONE SWAPS IN SULFUR BIOCHEMISTRY: Common artificial DNA

modification also occurs in nature

SULFUR SURPRISE

This dinucleotide, which occurs naturally in bacterial genomic DNA, possesses a sulfur atom in place of one of the nonbridging oxygen atoms on its phosphate group. O N HO

N

O –S

O

NH2

N

NH2

O

P

NH

N

O O

N

N N

OH

A

DNA MODIFICATION that was

originally conceived for the toolkits of biochemists and gene therapy researchers occurs naturally in bacteria (Nature Chem. Biol., DOI: 10.1038/nchembio.2007.39). The variation, in which a sulfur atom replaces one of the nonbridging oxygen atoms in a phosphate group that links DNA nucleotides together, is called phosphorothioation and is the first known physiological modification of DNA’s backbone. Microbiologist Zixin Deng and graduate student Lianrong Wang of Shanghai Jiaotong University, in China, and biological chemist Peter C. Dedon and postdoc Shi Chen of MIT unearthed the modification. The researchers confirmed the phosphorothioate’s chemical structure through high-performance liquid chromatography and mass spec-

TOXIC TURNDOWN POLLUTION: Big facilities in U.S.,

Canada cut releases more than small and mid-sized ones

Metals in toxic wastes are recycled.

PHOTO DISC

L

ARGER INDUSTRIAL facilities in the U.S. and Canada are doing a better job of reducing releases of toxic chemicals than are small and mediumsized plants, says an analysis released on Oct. 18. Cuts in waste generation by large facilities drove the drop in toxic releases in the U.S. and Canada between 1998 and 2004, according to an annual report from the North American Commission on Environmental Cooperation (CEC). The analysis combines data from the U.S. Toxics Release Inventory (TRI) and Canada’s National Pollutant Release Inventory. Big facilities have cut waste and emissions, but the same is not true of smaller plants. While they individually release smaller amounts of toxics than a big plant, small and mid-sized facilities as a group substantially increased their releases between 1998 and 2004, the analysis says. Large emitters, the report says, tend to participate in WWW.C E N- ONLI NE .ORG

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trometry. Though this is not the first natural appearance of sulfur in nucleic acids, the other cases occur mostly in RNA and involve modification on the heterocyclic bases as opposed to the backbone, Dedon says. Researchers have been making DNA bearing phosphorothioates for decades. Because this functional group confers stability against nucleases, which are enzymes that cleave DNA’s phosphate backbone, it has been useful for biochemical research and for clinical applications. “This result illustrates the principle that, ‘If man can do it, then nature has probably already done it long before,’ ” notes Paul R. Schimmel, a professor of molecular biology and chemistry at Scripps Research Institute. The newly reported work stems from over a decade of work by Deng, who previously characterized five enzymes that work together to incorporate sulfur into DNA. Many species of bacteria possess these enzymes, Dedon says, but no one has searched for them in higher organisms. The purpose of the newfound backbone motif is not yet known. Even so, “we are very excited about the implications of this observation,” Dedon says. The team suspects that phosphorothioation defends DNA against nucleases, much as methylation of DNA bases does. Phosphorothioation might also control gene expression. “It makes you wonder what other modifications of DNA are out there,” comments Richard J. Roberts, chief scientific officer of New England Biolabs, which sells nucleic acids, nucleases, and other biomolecules.—CARMEN DRAHL

pollution prevention programs, while smaller facilities are less likely to do so. “Industry and government action to limit chemical releases is showing steady progress,” says Adrián Vázquez-Gálvez, CEC’s executive director. Nonetheless, he says, “a large number of small and mediumsized industrial facilities need to do a better job in reducing their waste and emissions if we are going to see even greater progress in North America.” The report also finds that more than a third of the 3.12 million metric tons of toxics released in the U.S. and Canada during 2004 was moved to recycling facilities. Of all the toxic waste that was sent for recycling in the two countries that year, copper and its compounds composed 31%, zinc and its compounds accounted for 20%, and lead and its compounds made up 15%. Half of the two countries’ combined toxic releases in 2004 were emitted to the air, the CEC report adds. Vázquez-Gálvez says CEC is tracking the changes EPA made in late 2006 to TRI, which allows many U.S. facilities to provide fewer data about their toxic releases. Those changes leave Canada and Mexico with reporting systems that are “more sophisticated” than TRI, he tells C&EN. This could create pressure for those countries to follow EPA’s footsteps and cut down on the amount of information they collect, he says.— CHERYL HOGUE

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