Replication of Eukaryotic Chromosomes

Our research focuses on the mechanism of eukaryotic chromosome replication, using the budding yeasts Saccharomyces cerevisiae and Cryptococcus neoformans as model systems. We are currently working on three related projects on S. cerevisiae chromosome III replication. First, we unexpectedly found that derivatives of the chromosome lacking normal replication origins are maintained stably, suggesting that alternative mechanisms for initiating replication exist. Through analysis of mutants defective in the maintenance of the originless fragment and analysis of chromosome rearrangements, we have evidence that DNA repair pathways, and events that require telomeres all contribute to the maintenance of this chromosome. Second, we continue our systematic analysis of the structure of replication origins, and we have recently identified a new class of complex replication origins. Third, we are trying to understand why some replication origins that are active in plasmids are inactive in their normal chromosomal locations. In a new research program on the pathogenic basidiomycete Cryptococcus neoformans, we are studying centromeres and replication origins. This yeast is in a different phylum than the well-studied ascomycete yeasts, and there is a critical need for developing both basic information about its genome structure and improved tools for the molecular dissection of pathogenic determinants and potential drug targets.

Selected Publications

• Dershowitz, A., M. Snyder, M. Sbia, J. H. Skurnick, L. Y. Ong, and C. S. Newlon. 2007. Linear derivatives of Saccharomyces cerevisiae chromosome III can be maintained in the absence of autonomously replicating sequence elements. Mol Cell Biol 27:4652-63.
  
  
• Theis, J. F., A. Dershowitz, C. Irene, C. Maciariello, M. L. Tobin, G. Liberi, S. Tabrizifard, M. Korus, L. Fabiani, and C. S. Newlon. 2007. Identification of mutations that decrease the stability of a fragment of S. cerevisiae Chromosome III lacking efficient replicators. Genetics 177:1445-1458.
  
  
• Irene, C., Cioci, F., Maciariello, C., Camilloni, G., Newlon, C.S., and Fabiani, L., 2004, Identification of the sequences required for chromosomal replicator function in Kluyveromyces lactis. Mol. Microbiol. 51:1413-23.
  
  
• Theis, J.F., and Newlon, C.S. ,2001, Two compound replication origins in S. cerevisiae contain redundant origin recognition complex binding sites. Mol. Cell. Biol. 21:2790-2801.