Arne Stenlund
Associate Professor
Ph.D., Uppsala University, 1984
Papillomavirus; cancer; DNA replication
email stenlund@cshl.edu,
phone (516) 367-8407, fax (516) 367-8454
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.
Selected Publications
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. 2007. ATP-dependent minor groove recognition
of TA base pairs is required for template melting by the E1 initiator
protein. J. Virol.
81: 3293–3302.
Schuck, S., and Stenlund, A. 2006. Surface mutagenesis of the bovine
papillomavirus E1 DNA binding domain reveals residues required for multiple
functions related to DNA replication. J.Virol. 80:
7491–7499.
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.
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