Bernard P. Duncker

Associate Dean, Research

Bachelor of Science (BSc) Ottawa, Doctor of Philosophy (PhD) Queen's

Email: bduncker@uwaterloo.ca

Telephone: (519) 888-4567 ext. 33957

Office: Biology 1 291B

Research interests

My lab is using the budding yeast Saccharomyces cerevisiae in cancer-related studies of the cell cycle. We are currently focusing our 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 my laboratory is aimed at studying the way in which kinase complexes act at origins, and characterizing novel origin-associated proteins.

Selected publications

• Matthews, L.A., Jones, D.R., Prasad, A.A., Duncker, B.P. and Guarné, A. 2012. The structure of Saccharomyces cerevisiae Dbf4 motif N reveals a unique fold necessary for the interaction with Rad53. J. Biol. Chem. 287, 2378-2387

• Kim, D.R., Gidvani, R.D., Ingalls, B.P., Duncker, B.P. and McConkey, B.J. 2011. Differential chromatin proteomics of the MMS-induced DNA damage response in yeast. Proteome Sci. 9:62.
• Liu, M., Tee, C., Zeng, F., Sherry, J.P., Dixon, B., Bols, N.C. and Duncker, B.P. 2011. Characterization of p53 expression in rainbow trout. Comp. Biochem. Physiol. C 154, 326-332.
• Jones, D.R., Prasad, A.A., Chan, P.K. and Duncker, B.P. 2010. The Dbf4 motif C zinc finger promotes DNA replication and mediates resistance to genotoxic stress. Cell Cycle 9, 2018-2026.
• Matthews, L.A., Duong, A., Prasad, A.A., Duncker, B.P. and Guarné, A. 2009. Crystallization and preliminary X-ray diffraction analysis of motif N from Saccharomyces cerevisiae Dbf4. Acta Cryst. F65, 890-894.
• Duncker, B.P., Chesnokov, I.N., and McConkey, B.J. 2009. The origin recognition complex protein family. Genome Biol. 10, 214.
• Steinmoeller, J.D., Fujiki, K., Arya, A., Müller, K.M., Bols, N.C., Dixon, B. and Duncker, B.P. 2009. Characterization of rainbow trout CHK2 and its potential as a genotoxocity biomarker. Comp. Biochem. Physiol. C 149, 491-499.
• Cheng, Z., Duncker, B.P., McConkey, B.J. and Glick, B.R. 2008. Transcriptional regulation of ACC deaminase gene expression in Pseudomonas putida UW4. Can. J. Microbiol. 54, 128-136.
• Ingalls, B.P., Duncker, B.P., Kim, D.R. and McConkey, B.J. 2007. Systems level modeling of the cell cycle using budding yeast. Cancer Informatics 3, 367-380.
• Da-Silva, L.F. and Duncker, B.P. 2007. ORC function in late G1: maintaining the license for DNA replication. Cell Cycle 6, 128-130.
• Semple, J.W., Da-Silva, L.F., Jervis, E.J., Ah-Kee, J., Al-Attar, H., Kummer, L., Heikkila, J.J., Pasero, P. and Duncker, B.P. 2006. An essential role for Orc6 in DNA replication through maintenance of pre-replicative complexes. EMBO J. 25, 5150-5158.
• Varrin, A.E., Prasad, A.A., Scholz R., Ramer, M.D. and Duncker, B.P. 2005. A mutation in Dbf4 motif M impairs interactions with DNA replication factors and confers increased resistance to genotoxic agents. Mol. Cell. Biol. 25, 7494-7504.
• Semple, J.W. and Duncker, B.P. 2004. ORC-associated replication factors as biomarkers for cancer. Biotech. Adv. 22, 621-631.
• Duncker, B.P. and Brown, G.W. 2003. Cdc7 kinases (DDKs) and checkpoint responses : lessons from two yeasts. Mutation Research 532, 21-27.
• Pasero, P., Shimada, K. and Duncker, B.P. 2003. Multiple roles of replication forks in S phase checkpoints: sensors, effectors and targets. Cell Cycle 2, 568-572.
• Duncker, B.P., Shimada, K., Tsai-Pflugfelder, M., Pasero, P. and Gasser, S.M 2002. An N-terminal domain of Dbf4p mediates interaction with both Origin Recognition Complex (ORC) and Rad53p and can deregulate late origin firing. Proc. Natl. Acad. Sci. USA 99, 16087-16092.
• Gasser, S.M., Heun, P., Pasero, P. and Duncker, B.P. 2000. Regulation of the initiation of DNA replication in yeast by cis- and trans-acting factors. In: Cell Division and the Replicon, HFSP press.
• Duncker, B.P., Pasero, P., Braguglia, D., Heun, P., Weinreich, M. and Gasser, S.M. 1999. CyclinB/Cdk1 kinase stimulates ORC-and Cdc6-independent steps of semiconservative plasmid replication in yeast nuclear extracts, Mol. Cell Biol. 19: 1226-1241.
• Pasero, P., Duncker, B.P., Schwob, E. and Gasser, S.M. 1999. A role for the Cdc7 kinase regulatory subunit Dbf4p in the formation of initiation competent origins of replication. Genes & Dev. 13: 2159-2176.
• Duncker, B.P., Davies, P.L. and Walker, V.K. 1999. Increased gene dosage augments antifreeze protein levels in transgenic Drosophila melanogaster. Transgenic Res. 8: 45-50.
• Pasero, P., Duncker, B.P. and Gasser, S.M. 1999. In vitro replication in yeast nuclear extracts. Methods 18: 368-376.
• Braguglia, D., Heun, P., Pasero, P., Duncker, B.P. and Gasser, S.M. 1998. Semi-conservative replication in yeast nuclear extracts requires Dna2 helicase and supercoiled template. J. Mol. Biol. 281: 631-649.
• Duncker, B.P., Davies, P.L. and Walker, V.K. 1997. Introns boost transgene expression in Drosophila melanogaster. Mol. Gen. Genet. 254: 291-296.