The C-terminal third of UL42, a HSV-1 DNA replication protein, is dispensable for viral growth.
UL42 is the herpes simplex virus type 1 DNA polymerase (Pol) accessory protein and is required for viral DNA replication and growth. Previous results from this laboratory demonstrated that the N-terminal two thirds of the protein contains all of the biochemical activities of the protein which can be measured in vitro. These activities include dsDNA-binding, association with DNA polymerase, and stimulation of polymerase activity. To better understand the functions of UL42 in infected cells, we have isolated and characterized two viral recombinants, UL42lacZ and n338. In the mutant virus UL42lacZ, the UL42 gene was disrupted by insertion of the Escherichia coli lacZ gene, while in the mutant virus n338, a termination codon was introduced after amino acid position 338. Analysis of the mutant phenotypes suggest that (1) the first 338 residues of UL42 retain all the functions necessary for viral DNA replication and growth in lytic infection, (2) localization of UL42 to the cell nucleus is independent of Pol, and (3) localization of ICP8 (ssDNA-binding protein) to prereplication sites is independent of functional UL42.
Department of Virology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543.
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Gao
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DiTusa
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Cordingley
D000818:Animals; D001692:Biological Transport; D002451:Cell Compartmentation; D002467:Cell Nucleus / Q000378:metabolism; D004261:DNA Replication; D004279:DNA, Viral / Q000378:metabolism*; D004259:DNA-Directed DNA Polymerase; D005090:Exodeoxyribonucleases; D010641:Phenotype; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D017384:Sequence Deletion; D018139:Simplexvirus / Q000235:genetics / Q000254:growth & development*; D014709:Vero Cells; D014764:Viral Proteins / Q000096:biosynthesis / Q000235:genetics*; D001616:beta-Galactosidase / Q000096:biosynthesis
D004279:DNA, Viral; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins; D004259:DNA-Directed DNA Polymerase; D005090:Exodeoxyribonucleases; C043417:DNA polymerase, Simplexvirus; D001616:beta-Galactosidase