The E1 proteins
- Molecular Virology Laboratory, Institut de recherches cliniques de Montréal (IRCM), 110 Pine avenue West, Montreal, QC, Canada H2W 1R7 (Canada)
- Departments of Microbiology and Immunology, Biochemistry and the Witebsky Center for Microbial Pathogenesis, University of Buffalo, 210 Biomedical Research Building, School of Medicine and Biomedical Sciences, Buffalo, NY 14214 (United States)
E1, an ATP-dependent DNA helicase, is the only enzyme encoded by papillomaviruses (PVs). It is essential for replication and amplification of the viral episome in the nucleus of infected cells. To do so, E1 assembles into a double-hexamer at the viral origin, unwinds DNA at the origin and ahead of the replication fork and interacts with cellular DNA replication factors. Biochemical and structural studies have revealed the assembly pathway of E1 at the origin and how the enzyme unwinds DNA using a spiral escalator mechanism. E1 is tightly regulated in vivo, in particular by post-translational modifications that restrict its accumulation in the nucleus. Here we review how different functional domains of E1 orchestrate viral DNA replication, with an emphasis on their interactions with substrate DNA, host DNA replication factors and modifying enzymes. These studies have made E1 one of the best characterized helicases and provided unique insights on how PVs usurp different host-cell machineries to replicate and amplify their genome in a tightly controlled manner. - Highlights: • The papillomavirus E1 helicase orchestrates replication of the viral DNA genome. • E1 assembles into a double-hexamer at the viral origin with the help of E2. • E1 interacts with cellular DNA replication factors. • E1 unwinds DNA using a spiral escalator mechanism. • Nuclear accumulation of E1 is regulated by post-translational modifications.
- OSTI ID:
- 22436651
- Journal Information:
- Virology, Journal Name: Virology Journal Issue: 1-2 Vol. 445; ISSN VIRLAX; ISSN 0042-6822
- Country of Publication:
- United States
- Language:
- English
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