email leemor@cshl.edu, phone (516) 367-8821, fax (516) 367-8873

We study the molecular basis of cell regulatory processes by using the tools of structural biology and biochemistry to examine proteins and protein complexes associated with these processes. Our efforts largely center on nucleic acid regulatory processes.

The introduction of double-stranded RNA into a cell can trigger a gene silencing process called RNA interference (RNAi). Although there has been remarkable progress in unraveling the components of the RNAi machinery, we are just beginning to understand how they work at the molecular level. Therefore, we embarked on structural and biochemical studies of these proteins. By solving the structure of a full-length Argonaute protein, a key component in the RNAi machinery, we identified Argonaute as “Slicer”, the enzyme that cleaves the mRNA as directed by the siRNA. These studies enhance our understanding of this pathway, and should also improve the use of RNAi as a tool for gene knockdown technology.

Another system is DNA replication initiation in papillomaviruses. Papillomaviruses are DNA tumor viruses that cause benign and malignant lesions in humans. To gain insight into the mechanism of replication initiation, we are studying two viral proteins that are required for viral replication, the initiator E1 and the transcription factor E2, and their complexes. Based on crystal structures of the E1 hexameric helicase in complex with nucleotide and ssDNA as well as structures of DNA complexes of the DNA-binding domain, we presented a strand exclusion mechanism by sequential ATP hydrolysis for helicase activity of the initiator. This mechanism has wide implications for many oligomeric ATPases.

Please visit Leemor's Lab home page.

Selected Publications

Kumar, P. R., Yu, Y., Sternglanz, R., Johnston, S. A. and Joshua-Tor, L. 2008. NADP regulates the yeast GAL induction system. Science 319: 1090-1092.

Song, J.-J., Smith, S.K., Hannon, G.J., and Joshua-Tor, L. 2004. Crystal structure of Argonaute and its implications for RISC Slicer activity. Science 305: 1434–1437.