title: The E1 proteins.
abstract: 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.
authors.affiliation: Molecular Virology Laboratory, Institut de recherches cliniques de Montréal (IRCM), 110 Pine avenue West, Montreal, QC, Canada H2W 1R7; Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada.
authors.forename: Monika
authors.initials: M
authors.lastname: Bergvall
authors.forename: Thomas
authors.initials: T
authors.lastname: Melendy
authors.forename: Jacques
authors.initials: J
authors.lastname: Archambault
mesh_terms: D002467:Cell Nucleus / Q000821:virology; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D004261:DNA Replication; D004279:DNA, Viral / Q000235:genetics; D004789:Enzyme Activation; D016679:Genome, Viral; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D027383:Papillomaviridae / Q000201:enzymology* / Q000235:genetics / Q000502:physiology; D055503:Protein Multimerization; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D014779:Virus Replication
chemical_list: D004279:DNA, Viral; D009856:Oncogene Proteins, Viral; C084762:oncogene protein E1, Human papillomavirus type 18; D004265:DNA Helicases
keywords: ATPase; DNA replication; E1; Episome; Helicase; Papillomavirus; Phosphoryaltion; Post-translational modifications
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