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
1986 Proceedings of the National Academy of Sciences of the United States of America  
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
more » ... eft the transforming activity of DNA clones intact. A 481-bp Pst I-Sal I subclone ofBamHI-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+Crich sequences that are potential binding sites for transcription factor Spl, 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. Abbreviations: HSV-1 and HSV-2, herpes simplex virus types 1 and 2; bp, base pair(s); kb, kilobase(s).
doi:10.1073/pnas.83.20.7855 pmid:3020562 pmcid:PMC386821 fatcat:wuinugm6mfdnjfhhkpmsipuh2u