NEWS OF THE WEEK O
REIMAGINING LIFE’S CHEMICAL ENGINES BIOCHEMISTRY: Damaged DNA building block hints at the origins of life’s redox catalysts
B
Y STUDYING damaged DNA, researchers have
gained new insight about the possible predecessors of protein-bound cofactors, which help carry out the essential chemical reactions of life. They propose that in the so-called RNA world—an early period of life on Earth based on RNA instead of DNA—basic biochemistry might have been catalyzed by modified RNA building blocks, such as guanine. The hypothesis opens up a possible different dimension to the RNA world. “We’re asking the question— what were the plausible first steps” on the road to the small-molecule helpers of protein biochemistry today? says lead researcher Cynthia J. Burrows of the University of Utah. Burrows and graduate student Khiem Van Nguyen have observed that 8-oxo-7,8-dihydroguanine, an oxidatively damaged version of the base guanine, can mimic a flavin, a type of cofactor (J. Am. Chem. Soc., DOI: 10.1021/ja2072252). Specifically, the damaged base can catalyze the repair of another type of DNA damage—light-mediated dimerization—something a flavin-containing enzyme can also do. The researchers think the bases found in DNA and RNA were a likely evolutionary starting point for cofactors such as flavin adenine dinucleotide, a key player in the production of the energy source adenosine triphosphate. But plausible first steps on that evolutionary journey haven’t been defined. Flavins are effective catalysts in part because of their low redox potentials. Burrows, an expert in DNA damage, knew that 8-oxo-7,8-dihydroguanine possessed a
O
HN
O NH
H redox potential closer to N N O O N HN a flavin’s than to those of O Thymine canonical bases. So she and N dimer N H2N Nguyen incorporated the Modified guanine damaged base into synthetic DNA or RNA strands that contained a nearby thymine dimer, another UVB light type of DNA damage. With O O exposure to ultraviolet NH HN light, the modified guanine O H catalyzed cleavage of the N N N O O HN O thymine dimer, thereby Repaired N N H2N repairing the damage. thymines “I’d gotten used to the idea that any changes in the structure of DNA that could cause mutations are ‘damage’ and are bad, but DAMAGE CONTROL A modified that’s an outlook based on guanine attached to a short stretch of DNA life as we know it today,” catalyzes repair of a thymine dimer nearby. Burrows says. “I’m startThis is an unusual example of one type of ing to think that chemical DNA damage repairing another. modifications of bases could have been very useful 4 billion years ago,” before proteins emerged, she says. Burrows says the next steps will be to try to evolve the possible proto-flavin further in the lab, examine reaction conditions for the repair process that are more plausible for a primordial Earth, and explore reactivity of other modified bases. “If RNA catalysis predated protein catalysis, then what predated the enzyme cofactors that endow these [protein] biopolymers with their breadth of function?” asks Steven E. Rokita, who studies nucleic acid reactivity at the University of Maryland, College Park. Burrows and Nguyen’s work “presents a fascinating challenge to those interested in prebiotic chemistry and the RNA world,” he says. Moreover, the study also finds a beneficial function for a common type of DNA damage, he adds.—CARMEN
DRAHL
BUDGET Congress works on a stopgap funding measure for fiscal 2012 With days left until the start of fiscal 2012 and no final federal budget in sight, Congress has turned its attention to passing a short-term stopgap funding measure that would keep the government operating until Nov. 18. Introduced on Sept. 14, the continuing resolution (H.J. Res. 79) sets funding for all federal agencies at $1.043 trillion—the cap agreed to in August’s debt-ceiling legislation. This cap is 1.4% lower than the 2011 budget, meaning agencies across the board are likely to have less
money to work with until final appropriations are made. A vote on the measure is expected this week in both the House of Representatives and the Senate, as both chambers are scheduled to be in recess the last week of the month. President Barack Obama will need to sign the measure before Oct. 1, the start of fiscal 2012. “It is critical that Congress pass this [continuing resolution] and send it to the President as soon as possible,” said House Appropriations Committee Chairman Har-
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SEPTEMBER 19, 2011
old D. (Hal) Rogers (R-Ky.) in a statement. “The American people simply do not want or deserve—and our recovering economy can scarcely handle—the dangerous instability of a government shutdown.” To date, the House Appropriations Committee has cleared 11 of 12 annual appropriations bill, but the full House has passed only six of those. The Senate Appropriations Committee is working on the bills, but had cleared only four by C&EN’s press time. The full Senate hasn’t passed any of the measures.—SUSAN MORRISSEY
