Virology Lab
PCNA is homotrimer (as indicated by the three different colors) that provides processivity to cellular DNA polymerases and selectively recruits DNA repair and DNA damage response proteins to cellular DNA replication forks.
PDB file: 6gis |
Herpes is an incredibly common infection where most adults are infected with one of the nine human herpesviruses. In particular, Herpes simplex virus type 1 (HSV-1) infects over half of the United States population. Infections typically result in blisters on the skin, mouth, eyes, or genitals. The most common form of treatment is acyclovir, an antiviral that targets the viral DNA polymerase. This works via the viral thymidine kinase to phosphorylate and activate the drug. High doses and frequent drug administration increases antiviral resistance; therefore, the development of novel herpes antivirals that have a distinct mechanism of action is necessary.
The goal of my research is to determine how cellular host proteins contribute to maintaining the integrity of the viral genome and what factors are recruited to HSV-1 replication forks. This will show us how such interactions contributes to the regulation of replication, transcription, DNA structure, and viral genome integrity. Replication of the 152kbp double stranded genome occurs within the host nucleus and is catalyzed by viral replication machinery. This consists of a DNA polymerase (UL30), processivity factor (UL42), helicase primase complex, origin binding protein, and a single stranded DNA binding protein. Despite encoding a viral DNA polymerase processivity factor, our lab has found that host proliferating cell nuclear antigen (PCNA) interacts with HSV-1 DNA at replication forks and associates with viral DNA in a replication-dependent manner. Check out my lab's website at www.dembowskilab.com. |