The cellular DNA repair pathway is integral to maintaining genomic integrity and preventing the spread of deleterious mutations that can lead to cancer. We have observed that the Herpes Simplex Virus 1 (HSV-1) encoded Infected Cell Protein 0 (ICP0) interferes with the cellular DNA damage response by preventing the recruitment of DNA repair proteins to the sites of DNA damage. ICP0 is a RING domain E3 ubiquitin ligase and several observations in our lab lead us to believe that ICP0 may be ubiquitinating an as-yet-unknown cellular protein that is involved in the DNA repair pathway. My project in particular aims to determine the cellular targets of ICP0 by Tandem Affinity Purification and Mass Spectrometry identification of ICP0 interacting proteins. Thus far I have constructed a TAP-tagged ICP0 that has been successfully used to identify interacting proteins. I have also been able to determine that some of the identified targets are ubiquitinated by ICP0 and am in the process of determining whether any of the proteins may play a role in the recruitment of DNA repair proteins to sites of damage. These studies have the potential to identify new proteins involved in the DNA repair pathway as well as identify ubiquitination as a possible mechanism of DNA repair modulation. Thus, we may gain a greater understanding of the requirements for the successful repair of DNA damage and maintenance of genomic integrity.

PUBLICATIONS

Stoffel, A., Chaurushiya, M., Singh, B. and Levine, A. 2004. Activation of NF-kappaB and inhibition of p53-mediated apoptosis by API2/mucosa-associated lymphoid tissue 1 fusions promote oncogenesis. Proc. Natl. Acad. Sci U.S.A. 101(24): 9079-84.