Ph.D., Uppsala University, 1984
Papillomavirus; cancer; DNA replication
The research in our laboratory focuses on the DNA replication properties of papillomaviruses. Papillomaviruses constitute a very large family of viruses that infect and transform the basal epithelium in their hosts and that induce proliferation of cells at the site of infection. In most cases, the resulting tumors are benign and will usually regress after some time, but certain types of human papillomaviruses give rise to tumors that are prone to progress toward malignancy, frequently causing cervical carcinoma.
The DNA replication properties of papillomaviruses show some unique and interesting characteristics. As a part of their normal life cycle, these viruses can exist in a state of latency that is characterized by long-term maintenance of the viral DNA as a multicopy plasmid in the infected cells. The papillomavirus replication system thus provides a unique opportunity to study plasmid replication in mammalian cells.
Our research has two primary goals: (1) to acquire a detailed understanding of the processes required for DNA replication from the papillomavirus origin of replication, which is a requirement for understanding the viral life cycle; and (2) to use the papillomavirus replication system to gain a general understanding of DNA replication at the biochemical level. We are particularly interested in three universally required, fundamental processes for the initiation of DNA replication: (1) site-specific recognition of the origin of replication; (2) local strand separation or distortion; and (3) loading of a replication helicase.
Liu, X., Schuck, S., and Stenlund, A. 2010. Structure-based mutational analysis of the bovine papillomavirus E1 helicase domain identifies residues involved in the nonspecific DNA binding activity required for double trimer formation. J. Virol. 84: 4264–4276.Liu, X., and Stenlund, A. 2010. Mutaitons in Sensor 1 and Walker B in the bovine papillomavirus E1 initiator protein mimic the nucleotide bound state. J. Virol. 84: 1912–1919.
Liu, X., Schuck, S., and Stenlund, A. 2007. Adjacent residues in the E1 initiator _-hairpin define different roles of the _-hairpin in Ori melting, helicase loading, and helicase activity.Mol. Cell 25: 825–837.Schuck, S. and Stenlund, A. 2005. Assembly of a double hexameric helicase. Mol. Cell 20: 377–389.
Stenlund, A. 2003. Initiation of DNA replication: lessons from viral initiator proteins.Nat. Rev. Mol. Cell. Biol. 4: 777–785.