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David Clayton Opens Special Seminars Series

By Eddy Ball
October 2006

David Clayton
David Clayton described a comprehensive model of mtDNA replication. (Photo courtesy of Steve McCaw)

Sherine Chan and Bill Copeland
LMG Seminar Sponsor Sherine Chan and LMG Senior Investigator Bill Copeland listened with interest to the speaker's narrative of discoveries about mtDNA replication. (Photo courtesy of Steve McCaw)

On September 25 at 10:00 AM in Rodbell Auditorium, Laboratory of Molecular Genetics (LMG) researchers welcomed guest lecturer David A. Clayton, Ph.D., as the first speaker in its 2006-07 Special Seminars Series. Clayton, who is the vice president and chief scientific officer at the Howard Hughes Medical Institute (HHMI), spoke on "Mammalian Mitochondrial DNA Replication: What We Know" to an audience of NIEHS investigators and local area scientists. Sponsor Sherine Chan of LMG introduced Clayton and invited interested scholars to join the speaker for a brown bag lunch following the talk.

Clayton opened his talk by emphasizing the wealth of information yet to be discovered about mitochondrial DNA (mtDNA) replication. "I hope no one takes from the title 'what we know about mtDNA replication' that the seminar will be about three minutes long and we'll all be able to take an early lunch," he said. "Of course, what we don't want to see in the title is 'what we don't know' because that lecture would take all week, and I'd be here talking to myself."

The rest of Clayton's lecture focused on his laboratory's work elucidating the modes of mammalian mtDNA replication and transcription. Initial studies characterized the physical forms of closed circular supercoiled mtDNA from several mammalian species. This, in turn, permitted the analysis of replicative intermediates of mtDNA, principally by high resolution ultracentrifugation and electron microscopy techniques. Taking advantage of emerging technologies in molecular cloning facilitated the sequencing of the entire mouse mtDNA genome in 1981 and, subsequently, the discovery and characterization of proteins involved in transcription and replication.

Clayton explained that the mtDNA system has provided many surprises, including an altered genetic code, unusual forms of transfer RNAs and the formation of a novel RNA-DNA hybrid region with unusual stability. The 13 proteins encoded by mtDNA are essential for cellular vitality, and there are now many examples of human disorders owing to mutations and other defects in mtDNA.

In the course of his talk, Clayton reminded his audience of the need to use several platforms in research and to survey the literature exhaustively. Clayton, for example, used Atomic Force Microscopy, a more sensitive methodology, to investigate evidence of a strand-coupled model of mtDNA replication proposed by another lab. The newer methodology helped Clayton and his associates resolve the apparent contradiction and develop a more comprehensive model. By resisting the tendency among researchers to ignore older research, he observed, investigators can mine more data to support their conclusions and utilize insights that may have a stronger bearing on today's work than when they were initially published.

Prior to joining HHMI, Clayton was a professor of both pathology and developmental biology at Stanford University. He has made several highly significant contributions to the understanding of mtDNA replication and is an elected member of the Institute of Medicine of the National Academies. Furthermore, Clayton has been instrumental in the planning of the HHMI Janelia Farm Research Campus, which is a new interdisciplinary research facility fostering highly collaborative research.



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