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David Toczyski, PhD

David Toczyski, PhD
Professor, Cancer Research Institute
Research Summary:
Activation of the DNA damage checkpoint

The DNA damage response and ubiquitin-mediated proteolysis

The DNA damage response is a critical responder to environmental stress. We are using a combination of candidate approaches and phosphoproteomics to identify targets of the DNA damage response pathway that alter cellular physiology in response to DNA damage. These targets include regulators of origin firing, transcription, mitosis and histone modifications. 

Ubiquitination rivals phosphorylation in its widespread importance in many processes. Degradation, vesicular transport and the DNA damage response are all regulated by ubiquitination. Our lab has a long-standing interest in two ubiquitin ligases, the APC and the SCF. Both have important roles in cell cycle progression, as well as other processes. We have developed methods to identify substrates of these ligases, and are applying these to both yeast and human cells.

Selected Publications

Paulovich, A., Toczyski, D.P., and Hartwell, L.H. (1997) "When checkpoints fail". Cell 88 : 315-321.

Toczyski,D.P., Galgoczy, D.J., and Hartwell, L.H. (1997) " CDC5 and CKII Control Adaptation to the Yeast DNA Damage Checkpoint". Cell 90 : 1097-1106.

Galgoczy, D.J., and Toczyski, D.P. (2001) "Checkpoint adaptation precedes spontaneous and DNA damage-induced genomic instability in S. cerevisiae" MCB 21 : 1710-1718

Melo, J., Cohen, J. and Toczyski, D.P. (2001) "Two checkpoint complexes are independently recruited to sites of DNA damage in vivo " Genes and Development 15 : 2809-2821

Melo, J. and Toczyski, D. P. (2002) "The DNA damage checkpoint response" Current Opinions in Cell Biology 14: 237-245

Thornton, B. and Toczyski, D. P. (2003) "Cycling with the cyclosome: Securin and B cyclins are the only obligatory targets of the APC/C." Nature Cell Biology 5(12): 1090-4.

Thornton , B.R., Chen, K.C., Cross, F.R., Tyson, J.J., and Toczyski, D.P. (2004) "Cycling without the cyclosome: Modeling a yeast strain lacking the APC." The Cell Cycle 3(5): 629-33.

 Kaye, J., Melo, J. , Cheung, S.K., Vaze, M.B., Haber, J. and Toczyski, D. P. " DNA breaks promote genomic instability by impeding proper chromosome segregation " under review.