Human papillomaviruses (HPV) are causative agents in a host of human diseases including cervical cancer. My group studies the replication and transcriptional control of HPV16, the most commonly occurring virus in cervical cancer. Two proteins regulate HPV DNA replication, E1 and E2, while E2 also regulates transcription from the viral genome. We have identified several interacting proteins for E2 and have tested some of them in functional assays. The most likely candidate for mediating E2 function identified is TopBP1, a muti-BRCT domain containing protein that is involved in DNA replication and repair. Current work is determining whether this protein is essential for mediating E2 functions in transcription and/or replication. Other work in the lab has identified a treatment for enhancing the turnover of the E2 protein and we are currently trying to identify the cellular pathway responsible for this increased turnover. Identification of such a pathway will provide a therapeutic target for the treatment of HPV induced disease. We are also investigating the expression of TopBP1 in breast cancer (it is the most homologous protein to BRCA1) and have found aberrant expression of TopBP1 in a significant percentage of breast cancers. Currently we are trying to understand the mechanism behind the aberrant expression. We have also identified several chromatin modification domains encoded by TopBP1 and are currently identifying the cellular proteins responsible for mediating this activity.