David P. Bazett-Jones Professor

Ph.D., University of Toronto, 1981
Toronto Medical Discovery Tower Rm 15-307
416-813-2181
dbjones@sickkids.ca

Molecular and Cellular Imaging



Research Synopsis
The goal of my research program is to understand the structural basis for regulation of nuclear activities, such as gene transcription initiation and elongation. This knowledge is relevant to potential therapies that return regulatory mechanisms to the cell. One area of the program is to understand how DNA is organized by chromatin proteins. In particular, we are studying the protein complex called condensin. This molecular machine is responsible for compacting DNA into metaphase chromosomes.

A second area of investigation addresses the significance of PML (promyelocytic leukemia) bodies. There are approximately ten of these domains or bodies in a cell nucleus, and they are implicated in controlling cellular differentiation. We are characterizing their structure and composition in order to determine the molecular mechanisms by which they function.

Future Research
In the past year, we have learned how condensin compacts purified DNA fragments at the most fundamental level. We are now turning our attention to how this molecular machine interacts with nucleosomal DNA structures.

We also will try to determine how the PML subnuclear domains assemble and disassemble during the cell cycle. We also will investigate how viruses, such as HIV-1 and Adenovirus, and other cellular stresses, affect the integrity and function of these domains

   


Selected Publications
Kruhlak MJ, Hendzel MJ, Fischle W, Bertos N, Yange X.-J, Verdin E, Bazett-Jones DP. Regulation of acetylation in mitosis through loss of histone acetyltransferases and deacetylases from chromatin. J. Biol. Chem. 276: 38307-38319, 2001.

Boisvert F-M, Kruhlak MJ, Box A, Hendzel MJ, Bazett-Jones DP. The transcription co-activator CBP is a dynamic component of the PML nuclear body. J. Cell Biol. 152: 1099-1106, 2001.

Hendzel MJ, Kruhlak MJ, MacLean NAB, Boisvert F-M, Lever MA, Bazett-Jones, D.P. Compartmentalization of regulatory proteins in the cell nucleus. J. Steroid Biochem. Mol. Biol. 76: 9-21, 2001.

Kruhlak MJ, Levert MA, Fischle W, Verdin E, Bazett-Jones DP, Hendzel MJ. Mobility of the ASF splicing factor in live cells. J. Cell Biol. 150: 41-51, 2000.

Boisvert F-M, Hendzel MJ, Bazett-Jones DP. Promyelocytic Leukemia (PML) nuclear bodies are protein structures that do not accumulate RNA. J. Cell Biol. 148: 283-292, 2000.

Hendzel MJ, Boisvert F-M, Bazett-Jones DP. Direct visualization of a protein nuclear architecture. Molecular Biology of the Cell 10: 2051-2062, 1999.

Bazett-Jones DP, Côté J, Landel CC, Peterson CL, Workman JL. SWI/SNF complex creates loop domains in DNA and polynucleosome arrays and can disrupt DNA histone contacts within these domains. Mol. Cell. Biol.19: 1470-1478, 1999.

Hendzel MJ, Kruhlak MJ, Bazett-Jones DP. Organization of highly acetylated chromatin around sites of Hn RNA accumulation. Molecular Biology of the Cell 9: 2491-2507, 1998.

   

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