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Environmental Factor, November 2007, National Institute of Environmental Health Sciences

Wilson Gives Keynote Talk at Genome Stability Meeting

By Eddy Ball
November 2007

At the beginning of his talk, Wilson reinforced the networking/collaboration theme of the conference. “I’m looking forward to interacting with all of you.” (Photo courtesy of Steve McCaw)

NIEHS grantee Cordeiro-Stone, above, worked with Jinks-Robertson, Kunkel and Smart to organize the conference. (Photo courtesy of Steve McCaw)

Along with its impressive schedule of speakers, the conference was also notable for the time and attention it gave to postdocs and junior researchers. Shown here, left to right, are Laboratory of Molecular Genetics (LMG) Chief Jan Drake, LMG Visiting Fellow Miguel Garcia-Diaz, Ph.D., and Kunkel. (Photo courtesy of Steve McCaw)

Kunkel, right, closed his presentation file as Arana began her introduction of Wilson. Arana also staffed her poster, which reported on structure-function analysis of DNA binding. (Photo courtesy of Steve McCaw)

Former postdoctoral fellow Kirill Lobachev, Ph.D., right, now at the Georgia Institute of Technology, talked with his mentor, LMG Supervisory Research Geneticist Mike Resnick,Ph.D. Lobachev’s poster reported on his study of compromised replication fork progression. (Photo courtesy of Steve McCaw)

There is no mistaking the enthusiasm of Visiting Fellow Wenjian Ma, Ph.D., as he talks about his work in Resnick’s lab. Ma’s study examined a novel role for the yeast Pol32 subunit of DNA polymerase delta in BER. (Photo courtesy of Steve McCaw)

IRTA Fellow Zack Pursell, Ph.D., discussed ground-breaking work in the area of leading strand DNA replication performed in Kunkel’s lab. (Photo courtesy of Steve McCaw)

NIEHS grantee and conference presenter William Kaufmann took advantage of the poster session break to enjoy a cup of coffee as he looked at displayers’ abstracts. (Photo courtesy of Steve McCaw)

NIEHS Acting Director Sam Wilson, M.D., delivered the first of three keynote lectures at the October 13 “Determinants of Genome Stability in Human Disease” conference held in Chapel Hill at the William and Ida Friday Center for Continuing Education. The North Carolina regional conference and poster session was jointly sponsored by NIEHS, antibody supplier Abcam, Inc., the University of North Carolina (UNC) Lineberger Comprehensive Cancer Center, the Duke Comprehensive Cancer Center and North Carolina State University (NCSU).

Wilson was joined at the podium by NIEHS Laboratory of Structural Biology Chief and DNA Replication Fidelity Group Head Tom Kunkel, Ph.D., NIEHS Postdoctoral Fellow Mercedes Arana, Ph.D., and three Triangle-area NIEHS grantees: Conference Coordinator Marila Cordeiro-Stone, Ph.D., of UNC, her colleague William Kaufmann, Ph.D., and Robert Smart, Ph.D., of NCSU. Other speakers included National Institute of Diabetes and Digestive and Kidney Diseases Peggy Hsieh, Ph.D., Lawrence A. Loeb, M.D., Ph.D., of the University of Washington, Seattle, and Duke’s Thomas D. Petes, Ph.D., and Sue Jinks-Robertson, Ph.D.

Wilson’s talk was titled “Structural and Mechanistic Insights into Genome Protection through Base Excision Repair (BER).” The talk grew out of ongoing crystal–structure studies with his DNA Repair and Nucleic Acid Enzymology Group on repair pathways, sequential steps and substrates involved in the BER process.

“A whole range of events in the cell can lead to DNA damage that is repaired by BER,” Wilson began. “And we’re learning more and more every day about the importance of oxidative stress in inflammation and other processes. This type of stress leads to DNA damage, and this damage, in part, is repaired by BER.”

Throughout his talk, Wilson underscored the elaborate orchestration, the “fascinating system of complexity,” that takes place in the course of DNA repair. Better understanding of these mechanisms can help scientists gain insights into an organism’s failure to repair endogenous and environmentally induced damage to DNA, the effects of polymorphisms, such as ones affecting activity levels of the protein molecules XRCC1 and polymerase beta, and the ways these mechanisms relate to chemotherapy, such as the use of a DNA alkylating agent to combat tumor growth.

Wilson outlined the steps in the repair of DNA single-base lesions, including lesion removal, strand incision, gap filling, gap tailoring, flap removal and strand ligation. “There are many complexities and variations in each one of these steps,” he explained, “and there are many enzymatic redundancies. For example,… in the gap-filling step there are more than a dozen… enzymes [that] can, under appropriate conditions, conduct gap filling.”

Other speakers reported on mechanistic studies in yeast and specific mechanisms, such as mismatch repair and human replication fork protection complex. The talks progressed to the potential translational level with talks by Smart and Loeb on applications of genome stability research to human cancers.

Kunkel, whose lab was well-represented at the poster session, spoke briefly on the aims and focus of the conference. “The idea here, the primary objective,” he observed, “is to exchange unpublished and published information on the DNA transactions that determine genome stability, the mechanisms by which these transactions operate and how the failure of those DNA transactions are associated with human health consequences.”

Cordeiro-Stone’s remarks underscored the value of the meeting as a forum for regional investigators and as a networking/collaboration venue for postdocs and junior investigators. The meeting included two 90-minute poster sessions, showcasing a total of 41 abstracts and posters, a networking lunch and an evening reception. The format offered postdocs and junior investigators several opportunities for interacting with the speakers and with each other.

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