Louisa Gross Horwitz Prize - 2010

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Bruce Stillman, Ph.D., F.R.S.

A native of Australia, Bruce Stillman is a graduate of the University of Sydney and the Australian National University.  He moved to Cold Spring Harbor Laboratory as a Postdoctoral Fellow in 1979 and has been at the Laboratory ever since.  Dr. Stillman has been Director of the Cancer Center at Cold Spring Harbor since 1992, a position he still holds.  In 1994, he was appointed Director and in 2003 was appointed President of Cold Spring Harbor Laboratory.  Dr. Stillman’s research focuses on how chromosomes are duplicated in cells, a process that ensures accurate inheritance of genetic material from one cell generation to the next. Initially focusing on understanding the replication of DNA tumor viruses in mammalian cells, Dr. Stillman studied adenovirus and SV40 virus DNA replication. Stillman’s lab identified many core cellular DNA replication proteins and reconstituted SV40 DNA replication with purified proteins, thereby characterizing processes such as DNA polymerase clamp loading and switching from one DNA polymerase to another during DNA replication, a paradigm that is employed for many other DNA replication associated processes. Stillman also studied DNA-replication-coupled chromatin assembly and identified proteins required for inheritance of nucleosomes. Stillman and his colleagues then characterized the structure of chromosomal origins of DNA replication in the budding yeast S. cerevisiae and discovered the multi-subunit Origin Recognition Complex (ORC) that binds in an ATP-dependent manner to sites in chromosomes where initiation of DNA replication occurs.  ORC and other proteins load onto chromosomes competent protein complexes of MCM proteins that are used for initiation of DNA replication once the cell commits to cell division and enters S phase. Recently his lab and others have reconstituted pre-RC assembly in vitro with purified proteins and have characterized how the pre-RC is activated by cell cycle regulated protein kinases. Surprisingly, in mammalian cells ORC subunits also play roles in both centromere and centrosome activity during mitosis, thereby linking the initiation of DNA replication to processes that ensure accurate chromosome segregation.