Unwinding of the box I element of a herpes simplex virus type 1 origin by a complex of the viral origin binding protein, single-strand DNA binding protein, and single-stranded DNA.
The herpes simplex virus type 1 (HSV-1) genome contains three origins of replication: oriL and two copies of oriS. These origins contain specific sequences, box I and box II, linked by an AT-rich segment, that are recognized by an HSV-1-encoded origin binding protein (UL9 protein) which also possesses DNA helicase activity. Despite its intrinsic helicase activity, the UL9 protein is unable to unwind oriS or the box I element of oriS, either in the presence or absence of the HSV-1-encoded single-strand DNA binding protein, ICP8. However, a complex of the UL9 protein and ICP8 can unwind box I if it contains a 3' single-stranded tail at least 18 nt in length positioned downstream of box I. These findings suggest a model for the initiation of HSV-1 DNA replication in which a complex consisting of the UL9 protein bound to box I, and ICP8 bound to single-stranded DNA generated at the A+T rich linker, perhaps as a consequence of transcription, unwinds an HSV-1 origin of replication to provide access to the replication machinery with the consequent initiation of viral DNA replication. This mode of unwinding is distinct from that observed for other animal viruses--e.g., simian virus 40 or bovine papilloma virus--in which the initiator protein, T antigen, or E1 protein alone, unwinds elements of the origin sequence, and the single-strand DNA binding protein serves only to keep the separated strands apart.
Lee
S S
SS
Department of Biochemistry, Stanford University, CA 94305-5307, USA.
Lehman
I R
IR
D004277:DNA, Single-Stranded / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018259:Herpesvirus 1, Human / Q000235:genetics*; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism*
D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; C045462:ICP8 protein, Simplexvirus; D011994:Recombinant Proteins; D014764:Viral Proteins; C064565:UL9 protein, Human herpesvirus 1