title: Varicella-zoster virus (VZV) origin of DNA replication oriS influences origin-dependent DNA replication and flanking gene transcription.
abstract: The VZV genome has two origins of DNA replication (oriS), each of which consists of an AT-rich sequence and three origin binding protein (OBP) sites called Box A, C and B. In these experiments, the mutation in the core sequence CGC of the Box A and C not only inhibited DNA replication but also inhibited both ORF62 and ORF63 expression in reporter gene assays. In contrast the Box B mutation did not influence DNA replication or flanking gene transcription. These results suggest that efficient DNA replication enhances ORF62 and ORF63 transcription. Recombinant viruses carrying these mutations in both sites and one with a deletion of the whole oriS were constructed. Surprisingly, the recombinant virus lacking both copies of oriS retained the capacity to replicate in melanoma and HELF cells suggesting that VZV has another origin of DNA replication.
authors: Departments of Pediatrics and Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA, United States; Department of Molecular Biology, National Research Centre, El-Buhouth Street, Dokki, Cairo, Egypt. Electronic address: mkhalil2@stanford.edu.
authors: Mohamed I
authors: MI
authors: Khalil
authors: Departments of Pediatrics and Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA, United States.
authors: Marvin H
authors: MH
authors: Sommer
authors: Department of Microbiology and Immunology and The Witebsky Center for Microbial Pathogenesis and Immunology, University at Buffalo, Buffalo, NY, United States.
authors: John
authors: J
authors: Hay
authors: Department of Microbiology and Immunology and The Witebsky Center for Microbial Pathogenesis and Immunology, University at Buffalo, Buffalo, NY, United States.
authors: William T
authors: WT
authors: Ruyechan
authors: Departments of Pediatrics and Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA, United States.
authors: Ann M
authors: AM
authors: Arvin
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D002644:Chickenpox / Q000821:virology*; D004261:DNA Replication; D004279:DNA, Viral / Q000235:genetics*; D016679:Genome, Viral; D014645:Herpesvirus 3, Human / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D018741:Replication Origin; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
chemical_list: D004279:DNA, Viral; D014764:Viral Proteins
keywords: DNA replication; Flanking gene transcription; OriS; VZV