Of the more than 6,600 articles published in the Journal of Biological Chemistry (JBC) each year, fewer than 100 are featured as a "Paper of the Week." One of the papers recently selected for that honor features work from the lab of Dartmouth researcher Charles Brenner, Ph.D. The paper focuses on a particular protein associated with a rare neurological disease.

"We want to feature the exciting work our authors publish," says Robert Simoni, Ph.D., deputy editor of the JBC and chair of biological sciences at Stanford. "Reviewers are asked to nominate papers they judge to be in the top one to two percent of papers to be published in the JBC each year." Brenner's paper was selected, he adds, because of its "broad interest, novelty, and impact."

"We were the first people to identify an enzymatic activity of the Aprataxin protein," says Brenner, an associate professor of genetics and of biochemistry and a researcher at Dartmouth's Norris Cotton Cancer Center. It was already known that certain mutations in the gene that codes for Aprataxin result in malfunctioning versions of a protein that cause a rare inherited neurological disease called ataxiaoculomotor apraxia syndrome 1 (AOA1). AOA1 is characterized by loss of control over the movement of the head, eyes, and limbs.

Genes: But until now, no one understood how this protein worked. Then Brenner and his research colleagues—postdoctoral fellows Heather Seidle, Ph.D., and Pawel Bieganowski, Ph.D.—recognized similarities between a family of cancer-related genes and the ataxiaproducing gene and decided to investigate further. They found that mutated Aprataxin lacks a certain enzymatic function and that the "loss of that enzymatic activity leads to

Charles Brenner, right, and Pawel Bieganowski, center—pictured with grad student Huan Liu—were authors of a Journal of Biological Chemistry "Paper of the Week."

Photo by: Flying Squirrel Graphics

changes in the developing brain that produce the ataxia," Brenner explains.

Brenner hopes the attention generated by the "Paper of the Week" designation will "stimulate research into this very interesting protein in order to identify other molecules that are regulated by Aprataxin." Some of the molecules, he believes, "may turn out to be drug targets to treat the kids that are born with this disease."

Kristen Garner