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Environmental Factor, November 2015

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Aziz Sancar and Paul Modrich share Nobel Prize in chemistry

By John Yewell

Aziz Sancar

Sancar’s ability to generate knowledge about the molecular details of the process for repairing UV damage to DNA changed the entire research field, according to a statement by the Royal Swedish Academy of Sciences. (Photo courtesy of Max Englund)

Arnette and Sancar

Arnette, left, celebrated with Sancar, her former postdoc advisor, at UNC following the announcement of his receipt of the 2015 Nobel Prize in chemistry. (Photo courtesy of Laura Lindsey-Boltz)

Aziz Sancar, M.D., Ph.D., a longtime NIEHS grantee, was named a winner of the 2015 Nobel Prize in chemistry. He shares the award with Paul Modrich, Ph.D., from Duke University School of Medicine and the Howard Hughes Medical Institute, and Tomas Lindahl, Ph.D., from the Francis Crick Institute and Clare Hall Laboratory in Great Britain. All three were honored for their work on the mechanisms of DNA repair.

“I was very pleased to hear it,” Sancar told the Environmental Factor the day after getting the call from the Nobel committee. The award was also celebrated around the NIEHS campus. “We at NIEHS are thrilled to be able to support the vital work he is doing,” said Linda Birnbaum, Ph.D., director of NIEHS and the National Toxicology Program. “He is an extremely deserving candidate for the award.”

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Three approaches to studying DNA repair

Sancar is the Sarah Graham Kenan Professor of Biochemistry and Biophysics at the University of North Carolina at Chapel Hill School of Medicine (UNC). The Nobel committee honored Sancar for his work on two mechanisms that repair DNA damage. One mechanism involves the enzyme photolyase, which repairs the damage caused by ultraviolet (UV) light, which can cause skin cancer. The other is nucleotide excision, which repairs DNA strands damaged by carcinogenic substances, such as cigarette smoke and industrial pollution.

Modrich was recognized for his work recreating the molecular mechanism known as DNA mismatch repair, which corrects mismatched strands when DNA is copied. Modrich also has connections with NIEHS. He served on several review boards, including an external panel that reviews the work of NIEHS researchers, the Board of Scientific Counselors, from 1995 to 2000.

Lindahl’s work led to the first understanding of the instability of DNA. Although stable enough to allow for evolutionary change, DNA inevitably undergoes mutation, and certain proteins are used to effect repairs.

NIEHS support for study of nucleotide excision

In the last decade, NIEHS support of Sancar’s work has amounted to more than $1.6 million dollars. His current grant from NIEHS involves studying whether the removal of an oligonucleotide DNA fragment can lead to autoimmunity.

A prolific writer, Sancar has produced more than 350 scientific papers in his career. In May, Sancar and his team completed the monumental task of mapping the entire nucleotide excision repair system. “Out of six billion base pairs, pick out a spot and we’ll tell you how it is repaired,” he said.

Thomas Kunkel, Ph.D., principal investigator for the NIEHS DNA Replication Fidelity Group, remembers Sancar from way back. Kunkel joined NIEHS in 1982, the same year Sancar went to UNC, and they collaborated during the next six years.

“Aziz is a brilliant scientist whose exposure at a national and international level is primarily due to his prolific publication record, rather than attendance at meetings,” Kunkel said. “It’s particularly telling to win the Nobel Prize without spreading one’s gospel by personal appearance.” Kunkel added, “I know all three, and I’m thrilled for all of them.”

A well-deserved honor, say colleagues

Former colleagues were delighted at the news of Sancar’s prize. Robin Arnette, Ph.D., science editor in the NIEHS Office of Communications and Public Liaison, worked as a postdoctoral researcher for Sancar from 2000 to 2002. “Aziz has trained scores of graduate students and postdocs at UNC,” she said. “All of us are extremely proud of his accomplishment and grateful for his guidance and instruction.”

Bennett Van Houten, Ph.D., who served at NIEHS from 1999 to 2008, was among Sancar’s earliest postdoctoral fellows, joining his lab in 1984. Van Houten, also an NIEHS grantee studying DNA repair, is a professor of molecular oncology at the University of Pittsburgh and Carnegie Mellon University. “What makes him a scientist worthy of winning the Nobel Prize is his tremendous work ethic,” Van Houten said. “He has the ability to synthesize a huge amount of literature, develop highly productive collaborations, and be fearless taking on any project.”

(John Yewell is a contract writer for the NIEHS Office of Communications and Public Liaison)

nucleotide excision repair

Although Sancar considers his work on photolyase to be his most mechanistic and chemistry-related, he received the Nobel Prize in chemistry largely for his work on nucleotide excision repair, illustrated in this diagram from Royal Swedish Academy of Sciences. (Photo courtesy of the Royal Swedish Academy of Sciences)

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