Michael R. Botchan
University of California, Berkeley
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Primary Section: 21, Biochemistry Secondary Section: 22, Cellular and Developmental Biology Membership Type:
Member
(elected 2008)
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Research Interests
As a Biochemist and Molecular Biologist I have studied the fundamental mechanisms that allow for the creation of two DNA molecules from a single parental molecule- a process that underlies how "like begets like". I have used two different eukaryote models to further advance our understanding of these processes: vertebrate papilloma viruses of many types and the fruit fly Drosophila melanogaster. Genes often encode for protein activities that perform more than one function and we have uncovered such pleiotropy for the machinery critical to DNA replication. For the viruses our work showed that a viral encoded protein critical for gene expression (transcription of mRNA) binds site specifically to the viral chromosome and targets the viral encoded DNA replication initiator protein to a DNA site called an origin of DNA replication. From the early embryos of the fruit fly we purified a complex of proteins homologous to a yeast protein called Origin Recognition Complex (ORC) and showed that this ORC complex also needs other proteins with pleiotropic functions in gene expression to successfully assemble an active DNA replication machine. Unwinding of the double helix is a critical first step in the replication of DNA and our recent work shows that for cellular DNA replication a latent enzyme complex called the MCM complex is recruited to ORC before initiation and other protein factors activate the actual "helicase function".
