title: Assembly of a double hexameric helicase.
abstract: Viral initiators perform multiple functions in initiation of DNA replication including ori binding, melting, and unwinding, culminating in the formation of a double hexameric (DH) helicase. We have recapitulated the assembly of the papillomavirus E1 initiator DH helicase, providing the first description of how such a complex is formed. We have identified an intermediate, a double trimer (DT), which relies on two cooperating DNA binding activities to melt double-stranded DNA and generate a substrate for formation of the DH helicase. The formation of the DT is dependent on nucleotide binding, while formation of the DH also requires hydrolysable ATP. The DNA binding properties of the DT explain how E1, which binds to DNA as a dimer, can effect a transition to ring structures, such as the double hexamer. These results provide new insight into the intricate machinery that initiates DNA replication.
authors.affiliation: Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Schuck
authors.forename: Arne
authors.initials: A
authors.lastname: Stenlund
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D004265:DNA Helicases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004261:DNA Replication / Q000502:physiology*; D004279:DNA, Viral / Q000378:metabolism*; D027383:Papillomaviridae / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020836:Protein Structure, Quaternary / Q000502:physiology; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D004279:DNA, Viral; D014764:Viral Proteins; D000255:Adenosine Triphosphate; D004265:DNA Helicases