President & Professor
Ph.D., Australian National University, 1979
Every time a cell divides, it must accurately copy its DNA. With 3 billion “letters” in the human genome, this is no small task. My studies reveal the many steps and molecular actors involved, as well as how errors in DNA replication are involved in diseases that range from cancer to rare genetic disorders.
Bruce Stillman’s lab studies the process by which DNA is copied within cells before they divide in two. Working with yeast and human cells, Stillman and colleagues have identified many of the cellular proteins that function at the DNA replication fork during the S phase, the portion of the cell-division cycle when DNA synthesis occurs. Among these proteins are those that facilitate the assembly of chromatin, the protein–DNA complexes that form the chromosomes. Current research focuses on the mechanism that initiates the entire process of DNA replication in eukaryotic cells. At the heart of this mechanism is a protein that binds to “start” sites on the chromosomes, called the Origin Recognition Complex, ORC. The Stillman lab is part of an ongoing collaboration that determined the cryo-EM structure of ORC proteins in complex with a group of proteins, called a helicase, that unwind DNA during replication. These images offer molecular insights into how the helicase is loaded onto DNA. Stillman’s research also focuses on the process by which duplicated chromosomes are segregated during mitosis. They found ORC at centrosomes and centromeres, structures that orchestrate chromosome separation during mitosis. At centromeres, ORC subunits monitor the attachment of duplicated chromosomes to the mitotic spindle that pulls the chromosomes apart when they are correctly aligned. Stillman’s team has discovered that mutations in the Orc1 protein alter the ability of ORC to regulate both DNA replication and centrosome duplication. These mutations have been linked to Meier–Gorlin syndrome, a condition that results in people with extreme dwarfism and small brain size, but normal intelligence.
Stillman, Bruce (2015) Reconsidering DNA Polymerases at the Replication Fork in Eukaryotes. Molecular Cell 59(2) pp. 139-141.
Kara, N. and Hossain, M. and Prasanth, S. G. and Stillman, B. (2015) Orc1 Binding to Mitotic Chromosomes Precedes Spatial Patterning During G1 Phase and Assembly of the Origin Recognition Complex in Human Cells. J Biol Chem 290(19) pp. 12355-12369.
Hettmer, S. and Li, Z. and Billin, A. N. and Barr, F. G. and Cornelison, D. D. and Ehrlich, A. R. and Guttridge, D. C. and Hayes-Jordan, A. and Helman, L. J. and Houghton, P. J. and Khan, J. and Langenau, D. M. and Linardic, C. M. and Pal, R. and Partridge, T. A. and Pavlath, G. K. and Rota, R. and Schafer, B. W. and Shipley, J. and Stillman, B. and Wexler, L. H. and Wagers, A. J. and Keller, C. (2014) Rhabdomyosarcoma: Current Challenges and Their Implications for Developing Therapies. Cold Spring Harbor Perspectives in Medicine 4(11)
Sun, J. and Fernandez-Cid, A. and Riera, A. and Tognetti, S. and Yuan, Z. and Stillman, B. and Speck, C. and Li, H. (2014) Structural and mechanistic insights into Mcm2-7 double-hexamer assembly and function. Genes & Development 28(20) pp. 2291-303.
Mazurek, A. and Park, Y. and Miething, C. and Wilkinson, J. E. and Gillis, J. and Lowe, S. W and Vakoc, C. R and Stillman, B. (2014) Acquired Dependence of Acute Myeloid Leukemia on the DEAD-Box RNA Helicase DDX5. Cell Reports 7(6) pp. 1887-1899.Additional materials of the author at
CSHL Institutional Repository
Key step in molecular dance that duplicates DNA is deciphered
Protein involved in DNA replication, centrosome regulation linked to dwarfism, small brain size
2014 Herbert Tabor Research Award