Research Expertise and Interest

eukaryotic gene expression, drosophila chromosomes, papilloma viral DNA, chromosomal dynamics

Research Description

Michael Botchan is the Dean of Biological Sciences and professor of Biochemistry, Biophysics and Structural Biology.  Dr. Botchan’s scholarly work includes contributions to virology and unraveling the mechanisms of DNA replication where mammalian oncogenic viral DNA and chromosomal DNA from drosophila have been the focus. He discovered at CSHL that the oncogenic DNA virus SV-40 integrates into chromosomes in cells where DNA replication is either not robust or absent. In such cells the viral DNA joins to the host chromosome without DNA sequence dependence. This work presaged the discovery that such pathways are dependent upon randomly occurring breaks of the host chromosome and breaks within the viral DNA. At UC Berkeley his group revealed the mechanisms of papilloma virus DNA replication, including the cervical cancer causing human types. Following the discovery of the yeast initiator complex ORC made at CSHL the Botchan lab and colleagues at UC Berkeley showed that this complex was profoundly conserved in drosophila and the crystal structure of the fly complex ushered in the high-resolution structures of other homologues. DNA sequences chosen for start sites along the chromosome fiber are not determined by ORC’s hard wired sequence dependence as in the budding yeasts but chromatin structure and other accessory proteins are involved. Botchan’s group discovered the active form of the cellular helicase that unwinds the duplex drosophila DNA for sister strand copying which they named the CMG. The CMG is universally found throughout all eukaryotes.