Smith, Gerald

Genetic recombination plays a crucial role in the maintenance of chromosomal integrity and the generation of genetic diversity. During mitotic growth of cells, faithful repair of DNA double-strand breaks (DSBs) requires homologous recombination. Failure to repair DSBs is often lethal, as essential genes can be lost. During meiosis, recombination plays an important role in the proper segregation of chromosomes and the formation of viable sex cells. Aberrancies in recombination thus produce chromosomal losses and rearrangements, such as deletions and translocations, and can result in birth defects or cancers. Understanding the molecular mechanism of recombination will give us insight into the causes of these diseases and possibly ways of predicting or preventing them; it will also help create new cell lines and mutant organisms by gene targeting. Common features of recombination in model organisms, including easily studied microorganisms, aid identifying human genes for recombination and DSB repair, which may be altered in specific diseases such as cancer.

Our lab's goals are to elucidate how recombination and DSB repair are accomplished and how they are regulated to occur at the proper place and time. Our research is focused on meiotic recombination in the fission yeast Schizosaccharomyces pombe and on the major (RecBCD) pathway of recombination in the bacterium Escherichia coli. In both organisms we approach this problem genetically, by analyzing mutants altered in the process, and biochemically, by studying the enzymes and special DNA sites (hotspots) that promote recombination and repair. These approaches are greatly facilitated by the advanced genetics and biochemistry of these microorganisms.