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Bell, Stephen D.

Dr. Stephen D. Bell

Research Scientist
Molecular and Cellular Biochemistry Department
Indiana University Bloomington
Bloomington, IN

We are using evolution as a tool to dissect the molecular interactions underpinning the process of DNA replication. To achieve this we are exploiting the observation that during evolution, three principal phylogenetic Domains have appeared: Bacteria, Archaea and Eucarya. While the molecular machineries for the processes of DNA replication and transcription are fundamentally related between archaea and eukaryotes, the archaeal apparatus is in essence a stripped down version of that in eukaryotes. This simplicity, coupled with the conservation of the processes, render archaea a biochemically tractable, high-resolution model for the human DNA replication machinery.

The primary focus of my lab's research is the DNA replication machinery of hyperthermophilic archaeon Sulfolobus solfataricus. It is our aim to elucidate the biochemical basis of the mechanisms that underpin the initiation and elongation phases of DNA replication and to identify the conserved interaction interfaces between components of the machinery. To do this we have cloned, expressed and purified the Sulfolobus DNA replication proteins and identified origins of replication on the Sulfolobus chromosome. Using a combination of biochemical and molecular biological methods we have begun to determine the mode of action of these proteins and investigate their interactions both with each other and with the DNA template. We are now applying our findings to the human replication system.

  1. Characterization of an archaeal family 4 uracil DNA glycosylase and its interaction with PCNA and chromatin proteins
    Journal of Biochemistry, 2005
  2. Eukaryotic/Archaeal Primase and MCM Proteins Encoded in a Bacteriophage Genome
    Cell, 2005
  3. Origins of DNA replication in the three domains of life
    FEBS Journal, 2005
  4. Sir2 and the Acetyltransferase, Pat, Regulate the Archaeal Chromatin Protein, Alba
    Journal of Biological Chemistry, 2005
  5. Organization of the archaeal MCM complex on DNA and implications for the helicase mechanism
    Nature Structural & Molecular Biology, 2005
  6. Structure of the heterodimeric core primase
    Nature Structural & Molecular Biology, 2005
  7. The promiscuous primase
    Trends in Genetics, 2005
  8. Archaeal transcriptional regulation – variation on a bacterial theme?
    Trends in Microbiology, 2005
  9. Archaeal DNA Replication:A Robust Model for Eukaryotes
    Geothermal Biology and Geochemistry in YNP [TBI Text!], 2005
  10. Identification of Two Origins of Replication in the Single Chromosome of the Archaeon Sulfolobus solfataricus
    Cell, 2004
  11. The Heterodimeric Primase of the Hyperthermophilic Archaeon Sulfolobus solfataricus Possesses DNA and RNA Primase, Polymerase and 3'-terminal Nucleotidyl Transferase Activities
    Journal of Molecular Biology, 2004
  12. A Heterotrimeric PCNA in the Hyperthermophilic Archaeon Sulfolobus solfataricus
    Molecular Cell, 2003
  13. The Interaction of Alba, a Conserved Archaeal Chromatin Protein, with Sir2 and Its Regulation by Acetylation
    Science, 2002
  14. Holding it together: chromatin in the Archaea
    Trends in Genetics, 2002