Duke, UNC scientists win Nobel Prize in chemistry for work on DNA repair

UNC honors 2015 Nobel Prize of Chemistry scientists

Nobel Prize for Chemistry recipient Aziz Sancar addresses the audience during a press conference in the lobby of Marsico Hall Wednesday, October 7, 2015 in Chapel Hill, N.C. Sancar, the Sarah Graham Kenan Professor of Biochemistry and Biophysics a
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Nobel Prize for Chemistry recipient Aziz Sancar addresses the audience during a press conference in the lobby of Marsico Hall Wednesday, October 7, 2015 in Chapel Hill, N.C. Sancar, the Sarah Graham Kenan Professor of Biochemistry and Biophysics a

Professors from Duke and UNC-Chapel Hill won the Nobel Prize in Chemistry on Wednesday, prompting a joint celebration by rival universities and further evidence that the Research Triangle region lives up to its name.

The scientists – Paul Modrich of Duke and Aziz Sancar of UNC – won for their decades of work in understanding how cells repair damaged DNA. They share the $960,000 prize with Swedish scientist Tomas Lindahl, an emeritus leader at Francis Crick Institute and emeritus director of Cancer Research UK at Clare Hall Laboratory in England.

The Royal Swedish Academy of Sciences said the scientists’ work “has provided fundamental knowledge of how a living cell functions” and can be used for the development of new ways to treat cancer. Though they conduct research in the same general field, the three men worked independently on the discoveries that earned them the Nobel.

Modrich, 69, is the James B. Duke professor of biochemistry at Duke’s medical school and a member of the Duke Cancer Institute. He’s also an investigator with the Howard Hughes Medical Institute. Turkish-born Sancar, 69, is the Sarah Graham Kenan professor of biochemistry at UNC’s medical school. He is only the second Turk to win a Nobel Prize.

Leaders from the two universities teamed up in Chapel Hill for a news conference at a research building decorated with Carolina blue and Duke blue balloons. The Nobel winners were humble, almost speechless, at their accomplishment. They gave credit to their own faculty mentors and their graduate students, some of whom sat in the front row, shooting video with mobile phones.

“I’ve been stunned by this,” said Modrich, speaking by phone from a remote cabin in New Hampshire, where he and his wife were vacationing and had planned to go canoeing Wednesday. “It’s overwhelming.”

Sancar and Modrich have collaborated on a few research papers and occasionally dine together, but their work is on separate aspects of DNA repair.

“He may not know this – even though we all hate Duke – I have been nominating him for the last, I would say, 10 years for the Nobel Prize,” Sancar said of his colleague in Durham.

Sancar also used the moment to remember his homeland, Turkey, where his town is near the border with Syria. He asked everyone to remember the humanitarian crisis in the region and work “towards peaceful solutions and scientific approaches to our problems rather than concentrating on things that divide us.”

Shortly after stepping down from the stage, Sancar was whisked upstairs to a quieter room to wait for a congratulatory call from Turkey; he later talked to the country’s prime minister.

Wednesday’s announcement marked a second Nobel for UNC and a second for Duke. UNC’s Oliver Smithies won the prize for medicine in 2007, and Duke’s Robert Lefkowitz won the chemistry prize in 2012.

“It’s a special moment for two very proud institutions,” UNC Chancellor Carol Folt said. “And I think we love the fact that we’re connected at this moment.”

Michael Kastan, executive director of the Duke Cancer Institute, said a concentration of Nobel Prize winners can help Duke, UNC and the region attract more top scientists. But there is a greater purpose, too. “It’s great for the Triangle, it’s great for the universities, but more importantly, it’s great for our patients,” Kastan said.

The recognition of the field of DNA repair is overdue, Kastan added.

“DNA damage causes cancer. DNA damage is used to treat cancer with radiation therapy and chemotherapy. And DNA damage causes the side effects of cancer treatment,” he said. “It can’t get more important for cancer than that. The three individuals that are being honored with the Nobel Prize this year have made extraordinary contributions in our understanding of the DNA repair process.”

The three individuals that are being honored with the Nobel Prize this year have made extraordinary contributions in our understanding of the DNA repair process.

Michael Kaston, executive director, Duke Cancer Institute

Human DNA, which contains our genes, is constantly under assault from ultraviolet rays from the sun and carcinogenic substances. When DNA is damaged, cancer and other diseases can develop.

DNA was thought to be a stable molecule until the 1970s when Lindahl showed that it decays at a rate that seemed incompatible with human life. He realized that there must be a built-in repair mechanism, opening a new field of research.

Modrich’s key contribution has been the identification of a mismatch repair system, in which a cell’s proteins “proofread” and correct rare errors that occur in the DNA code during chromosome replication. The discovery also led scientists to the genes for the most common form of colon cancer and about 20 to 30 percent of other spontaneous tumors, as well as Huntington’s disease and other neurodegenerative disorders.

Sancar mapped the mechanism that cells use to repair UV-damaged DNA. Earlier this year, his team created a DNA repair map of the entire human genome.

“Now we can say to a fellow scientist, ‘Tell us the gene you’re interested in or any spot on the genome, and we’ll tell you how it is repaired,’” Sancar said in May, when the mapping was announced by UNC. “Out of six billion base pairs, pick out a spot and we’ll tell you how it is repaired.”

The work of Modrich and Sancar dates back to the 1970s, when they were young student researchers. Both continue to work in the same field as their wives, who are also scientists.

“Imagine you’ve spent 40 years on something,” Gwen Sancar said Wednesday. “This is recognition that you were not crazy, that what you’ve done absolutely matters, that you probably have affected the advancement of science and helped mankind.”

In an interview with the Howard Hughes Medical Institute, Modrich said he liked the problem-solving aspect of research. “I get a lot of satisfaction from the small steps,” he said.

Modrich is continuing his investigation of mismatch repair systems (MMR) in humans, including its role in cancer resistance to chemotherapy. Basic research leads to crucial findings for human health, he said.

“Had we not had a basic knowledge of MMR in bacteria, we wouldn’t have guessed that defects in the human pathway were the cause of hereditary colon cancer,” Modrich said in the Howard Hughes interview. “That is why curiosity-based research is so important. You never know where it is going to lead. … A little luck helps, too.”

Paul Modrich


Aziz Sancar

Modrich and Sancar will travel to Stockholm to receive their prizes on Dec. 10, the anniversary of prize founder Alfred Nobel’s death in 1896.

Folt joked that she called Sancar in his lab Wednesday and told him she had even better news for him: a free lifetime parking pass at UNC, just as Smithies received in 2007.

“So I thought that was pretty good, right?” Folt said. “And then he laughed and said I have an even bigger surprise for you: I don’t drive.”

When asked what was next for him, Sancar said his research team is feverishly working to submit a proposal to the National Institutes of Health for more grant funding.

He’s hoping NIH will take a serious look at it.

The Associated Press contributed to this report.

Jane Stancill: 919-829-4559, @janestancill

Previous Nobel Prize winners from the Triangle

Robert J. Lefkowitz of Duke University shared the 2012 Nobel Prize for chemistry with Stanford University researcher Brian K. Kobilka, whom Lefkowitz had trained in the 1980s. They were recognized for discoveries about how the body’s cells respond to outside signals – a key to the workings of beta blockers, antihistamines and as many as half of all prescription medications.

Oliver Smithies, professor of pathology and laboratory medicine at UNC-Chapel Hill, won the prize in physiology or medicine in 2007 for “discoveries of principles for introducing specific gene modifications in mice by the use of embryonic stem cells.”

Martin Rodbell, National Institute of Environmental Health Sciences in Research Triangle Park, won the prize in physiology or medicine in 1994 “for their discovery of G-proteins and the role of these proteins in signal transduction in cells.” Rodbell died in 1998.

Gertrude B. Elion and George H. Hitchings of the Wellcome Research Laboratories in RTP won the prize for physiology or medicine in 1988 “for their discoveries of important principles for drug treatment.” Hitchings died in 1998; Elion died in 1999.

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