Bernard Duncker

Professor Duncker's lab is using the budding yeast Saccharomyces cerevisiae in cancer-related studies of the cell cycle. They are currently focusing their investigations on identifying and characterizing protein factors that control the initiation of DNA replication.

S. cerevisiae has proven to be a very useful organism for such studies because it is one of the few eukaryotes for which origins of replication have been well characterized, and the only one for which an origin consensus sequence has been identified.

These findings, in combination with an advanced knowledge of budding yeast genetics, has permitted the identification of numerous protein factors that associate with replication origins. These include members of the pre-replicative complex (pre-RC), which assembles at origins during G1 phase of the cell cycle. The pre-RC must be present in order for origins to fire and is rapidly disassembled in S phase. In addition to the pre-RC, the activity of two protein kinase complexes Clb/Cdc28 and Dbf4/Cdc7 are required to trigger replication.

Homologues for these proteins have been found in a wide variety of organisms, including humans, and have demonstrated promise as diagnostic markers for cell proliferation in potential malignancies.

Work in Professor Duncker's laboratory is aimed at studying the way in which kinase complexes act at origins, characterizing novel origin-associated proteins, and determining how these protein factors are regulated when cell cycle checkpoints are triggered.