Initiation of new DNA strands by the herpes simplex virus-1 primase-helicase complex and either herpes DNA polymerase or human DNA polymerase alpha

J Biol Chem. 2009 Jan 16;284(3):1523-32. doi: 10.1074/jbc.M805476200. Epub 2008 Nov 20.


A key set of reactions for the initiation of new DNA strands during herpes simplex virus-1 replication consists of the primase-catalyzed synthesis of short RNA primers followed by polymerase-catalyzed DNA synthesis (i.e. primase-coupled polymerase activity). Herpes primase (UL5-UL52-UL8) synthesizes products from 2 to approximately 13 nucleotides long. However, the herpes polymerase (UL30 or UL30-UL42) only elongates those at least 8 nucleotides long. Surprisingly, coupled activity was remarkably inefficient, even considering only those primers at least 8 nucleotides long, and herpes polymerase typically elongated <2% of the primase-synthesized primers. Of those primers elongated, only 4-26% of the primers were passed directly from the primase to the polymerase (UL30-UL42) without dissociating into solution. Comparing RNA primer-templates and DNA primer-templates of identical sequence showed that herpes polymerase greatly preferred to elongate the DNA primer by 650-26,000-fold, thus accounting for the extremely low efficiency with which herpes polymerase elongated primase-synthesized primers. Curiously, one of the DNA polymerases of the host cell, polymerase alpha (p70-p180 or p49-p58-p70-p180 complex), extended herpes primase-synthesized RNA primers much more efficiently than the viral polymerase, raising the possibility that the viral polymerase may not be the only one involved in herpes DNA replication.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • DNA Helicases / metabolism*
  • DNA Polymerase I / metabolism*
  • DNA Primase / metabolism*
  • DNA Primers / metabolism
  • DNA, Viral / biosynthesis*
  • DNA-Directed DNA Polymerase / metabolism*
  • Exodeoxyribonucleases / metabolism*
  • Herpesvirus 1, Human / physiology*
  • Humans
  • RNA / metabolism
  • Viral Proteins / metabolism*
  • Virus Replication / physiology*


  • DNA Primers
  • DNA, Viral
  • RNA primers
  • Viral Proteins
  • RNA
  • DNA Primase
  • DNA Polymerase I
  • DNA-Directed DNA Polymerase
  • Exodeoxyribonucleases
  • helicase-primase, Human herpesvirus 1
  • DNA polymerase, Simplexvirus
  • DNA Helicases