Localization and comparative nucleotide sequence analysis of the transforming domain in herpes simplex virus DNA containing repetitive genetic elements

C. Jones, J. Ortiz, R. J. Jariwalla

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

The 7.5-kilobase BamHI E fragment (BamHI-E) of herpes simplex virus type 2 (HSV-2) DNA (map position 0.533-0.583) encodes the 144-kDa subunit of ribonucleotide reductase and induces the neoplastic transformation of immortalized cell lines. To define the minimal transforming region of BamHI-E, a series of subclones were constructed that spanned the entire fragment. These subclones were assayed for focus formation in Rat-2 cells. Removal of the promoter region from the viral 144-kDa-protein gene left the transforming activity of DNA clones intact. A 481-bp Pst I-Sal I subclone of BamHI-E was capable of inducing focus formation and tumorigenic conversion. The nucleotide sequence of this fragment and the colinear nontransforming region of HSV-1 DNA was determined and compared. Striking differences were detected in the structure and organization of repeated sequence elements. Specifically, transforming HSV-2 DNA contains multiple regions of alternating purines and pyrimidines, G+C-rich sequences that are potential binding sites for transcription factor Sp1, and insertion-like sequence elements that are interrupted by base substitutions in nontransforming HSV-1 DNA. These results define a distinct transforming domain in HSV-2 DNA composed of repetitive elements implicated in gene rearrangement and activation.

Original languageEnglish (US)
Pages (from-to)7855-7859
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume83
Issue number20
DOIs
StatePublished - Jan 1 1986

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Simplexvirus
Sequence Analysis
Human Herpesvirus 2
DNA
Human Herpesvirus 1
Sp1 Transcription Factor
Ribonucleotide Reductases
Pyrimidines
Purines
DNA Transposable Elements
Gene Rearrangement
Oncogenes
Genetic Promoter Regions
Transcriptional Activation
Clone Cells
Binding Sites
Cell Line
Proteins

ASJC Scopus subject areas

  • General

Cite this

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title = "Localization and comparative nucleotide sequence analysis of the transforming domain in herpes simplex virus DNA containing repetitive genetic elements",
abstract = "The 7.5-kilobase BamHI E fragment (BamHI-E) of herpes simplex virus type 2 (HSV-2) DNA (map position 0.533-0.583) encodes the 144-kDa subunit of ribonucleotide reductase and induces the neoplastic transformation of immortalized cell lines. To define the minimal transforming region of BamHI-E, a series of subclones were constructed that spanned the entire fragment. These subclones were assayed for focus formation in Rat-2 cells. Removal of the promoter region from the viral 144-kDa-protein gene left the transforming activity of DNA clones intact. A 481-bp Pst I-Sal I subclone of BamHI-E was capable of inducing focus formation and tumorigenic conversion. The nucleotide sequence of this fragment and the colinear nontransforming region of HSV-1 DNA was determined and compared. Striking differences were detected in the structure and organization of repeated sequence elements. Specifically, transforming HSV-2 DNA contains multiple regions of alternating purines and pyrimidines, G+C-rich sequences that are potential binding sites for transcription factor Sp1, and insertion-like sequence elements that are interrupted by base substitutions in nontransforming HSV-1 DNA. These results define a distinct transforming domain in HSV-2 DNA composed of repetitive elements implicated in gene rearrangement and activation.",
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