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.
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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.