Robert E Malone Ph.D.

Robert E Malone Ph.D.
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We study genetic recombination as it occurs in meiosis. The first unique step that occurs in the meiotic pathway is recombination and pairing of homologous chromosomes. We wish to understand the enzymes that catalyze the exchange event, the genes that code for those enzymes, the sequences in the DNA that act as recombination hot spots, the molecular mechanism of the recombination event, and how the cell insures that recombination precedes the first division. We study a simple organism, baker's yeast (Saccharomyces cerevisiae). Because yeast is a true eukaryote and goes through meiosis just like Mendel's peas what we learn about meiotic recombination in yeast will be relevant to all eucaryotes, including man. We approach the problem of recombination from several directions. First, we study genes that code for functions involved in starting recombination. We have discovered, cloned, sequenced, and are studying several such REC genes. We now know the order of action of many genes in the recombination process. We are using a combination of molecular and genetic approaches to understand the functions that act in recombination. Second, we study the genetic pathway for chromosome exchange and pairing. By this we mean knowing which gene acts at each point, and how many different paths there are. Currently we have classified genes into three classes: Early and late recombination, and synapsis genes. We also have found that the initiation of recombination sends a signal to delay the first meiotic division and are working on determining how that "intracellular signal transduction" process works. This work should be relevant to the types of decisions cells make in other developmental paths. Third, we are studying recombination to determine the role of the DNA as the substrate. Recombination is not distributed randomly along the chromosome; there are sites that act as recombination hot spots. Given the hundreds of thousands of base pairs in a chromosome, how is it that chromosomes always line up properly and exchange exactly the right parts? We feel that the hot spots represent DNA sequences that play an important role in this initiation process. Future work will join our research with the hot spots to our research on meiotic recombination functions.

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Research Paradigm(s): 
Cell Cycle/replication/recombination
Cellular Signalling Pathways
Development and Dysmorphology
Yeast and Fungi
College of Liberal Arts and Sciences