title: A functional interaction of ICP8, the herpes simplex virus single-stranded DNA-binding protein, and the helicase-primase complex that is dependent on the presence of the UL8 subunit.
abstract: The herpes simplex virus type 1 (HSV) single-stranded DNA-binding protein (SSB, ICP8) stimulates the viral DNA polymerase (Pol) on an oligonucleotide-primed single-stranded DNA template. This stimulation is non-specific since other SSBs also increase Pol activity. However, only ICP8 was stimulatory when Pol activity was dependent upon priming by the viral helicase-primase complex. ICP8 also specifically stimulated the primer synthesis and ATPase activities of the helicase-primase. The mechanism of stimulation was different from that of Pol; helicase-primase stimulation required much lower amounts of ICP8 than the amount that saturates the DNA and optimally stimulates Pol. Furthermore, ICP8 did not act by removing secondary structure as stimulation also occurred on homopolymer templates. While the UL8 component of the helicase-primase is not required for enzymatic activities by a subassembly of the UL5 and UL52 proteins, only the holoenzyme (UL5/8/52) was stimulated by ICP8. These results identify a unique, functional interaction between the ICP8 SSB and the helicase-primase complex, mediated by the UL8 subunit.
authors.affiliation: Department of Virology, Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, CT 06492, USA. Robert-K-Hamatake@BMS.com
authors.forename: R K
authors.initials: RK
authors.lastname: Hamatake
authors.forename: M
authors.initials: M
authors.lastname: Bifano
authors.forename: W W
authors.initials: WW
authors.lastname: Hurlburt
authors.forename: D J
authors.initials: DJ
authors.lastname: Tenney
mesh_terms: D004265:DNA Helicases / Q000378:metabolism*; D019915:DNA Primase; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004789:Enzyme Activation; D018259:Herpesvirus 1, Human / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C045462:ICP8 protein, Simplexvirus; D014764:Viral Proteins; D019915:DNA Primase; C062021:helicase-primase, Human herpesvirus 1; D004265:DNA Helicases