- B.S., Biology, University of Connecticut, 1979
- Ph.D., Genetics, Harvard University, 1989
- Postdoc., University of California, San Francisco
Research Interests:Current research is focused on understanding how sequence-specific DNA binding proteins regulate the initiation of eukaryotic DNA replication and contribute to genome stability. The Tetrahymena ribosomal DNA (rDNA) minichromosome is being studied as a model because this chromosome is amplified 10,000 fold within a single S phase during development and is replicated only once per cell cycle during subsequent cell divisions. Recent studies have established a new paradigm for DNA recognition by the conserved, multi-subunit eukaryotic origin recognition complex (ORC). Tetrahymena
ORC contains an integral RNA subunit that forms Watson-Crick base pairs with regulatory sequences at the rDNA origin. This RNA, designated 26T, is derived from the 3’ end of 26S ribosomal RNA, revealing an unprecedented role for ribosomal RNA in chromosome biology. The biogenesis of 26T RNA may coordinate DNA replication with cellular metabolism. A second origin binding factor, TIF1, regulates the timing of rDNA replication initiation and has an additional, essential role in activation of the intra-S phase DNA damage checkpoint response.
Shibani DattaPamela Sandoval