"Exploring DNA Repair Pathways & Stem Cell-Like Behavior in Budding Yeast"
Wednesday, November 19, 2008
P&S Alumni Auditorium
650 West 168th Street, First Floor
Rodney Rothstein received his B.S. from the University of Illinois, Chicago, in 1969 and his Ph.D. from the University of Chicago in 1975, where he started his studies on yeast genetics in 1970. He did postdoctoral work at the University of Rochester and Cornell University before taking a position as Assistant Professor of Microbiology at UMDNJ-Newark (1979-84). He joined Columbia University Medical Center in 1984 and was promoted to full Professor in 1998. He has had appointments at the University of Paris VI (1992), Université René Descartes, Faculté de Médicine Necker Enfants Malades (1999) and at Institut Curie, Paris (Mayent-Rothschild Boursier, 2005). He has been a member of numerous advisory panels for the Damon Runyon-Walter Winchell Cancer Fund, the NSF, the NIH and was a member of National Advisory Council for Human Genome Research from 1993-97. He has chaired numerous meetings on Genetic Recombination and Genome Stability. In 2001, he gave the Erasmus Lecture at Erasmus University in Rotterdam, the Netherlands. In 2005 he gave the Herbert Stern Lecture at UC San Diego. In 2006 he gave the Gregor Mendel Lecture at Mendel’s Abbey, Brno, Czech Republic, and this year he gave keynote lectures at the Salk Institute’s DNA Replication & Genome Stability meeting in La Jolla, California and at the Conférences Jacques Monod’s Biological Response to DNA Damage meeting in Roscoff, Brittany, France.
Rodney Rothstein pioneered the use of recombination to alter genomes and has used these methods to isolate novel genes involved in the maintenance of genome stability. His work on plasmid-chromosome recombination led to the double-strand break repair model for genetic recombination, a major paradigm shift. His development of “one-step” gene disruption technology is an elegant method noteworthy for the ability to create a non-reverting null mutation, which is critical for defining gene function. Rothstein’s work directly led to the “knock-out” technology that is used in many organisms to exploit recombination to either remove or insert DNA sequences into specific positions within the genome. In yeast, this technique led to the creation of a gene disruption library, the first complete collection of gene knock-outs for an entire eukaryotic genome. His laboratory has gone on to discover many new genes that affect the control of genome stability and are conserved in most species. Among them are Top3, a novel type I topoisomerase and Sgs1, a DNA helicase whose human homologues (Blm, Wrn and Rts) cause cancer predisposition and premature aging. Rothstein’s lab also showed that active pol II transcription elevates recombination between directly repeated sequences, which are often targets for disease-associated chromosome rearrangements. His work on Holliday junction recombination intermediates in the ribosomal DNA showed that replication and recombination are intimately associated, an area of intense study today. His lab has also applied the powerful tools of fluorescent microscopy and cell biology to address the coordination of recombination events. They showed that the central yeast recombination protein, Rad52, is responsible for the recruitment of other DNA repair proteins to recombination foci. By fluorescently marking the broken ends of chromosomes, they demonstrated for the first time that recombination foci assemble at these DNA ends. His lab also found that these foci act as repair centers capable of repairing more than one DSB. His work on the choreography of the DNA damage response using a combination of genetics and cell biology has set a new standard for the study of DNA damage-induced foci in all organisms. Recently, he has shown that yeast spores exhibit a unique asymmetric pattern of protein segregation reminiscent of a stem cell-like division showing that microbial systems likely laid the foundations for stem cell behavior.
In summary, Rodney Rothstein’s research is remarkable for its breadth and originality. His work has touched almost every aspect of the cellular response to DNA damage and his lab has uncovered many new and important pathways that eukaryotic cells use to cope with this problem.