DNA sequence studies of simian virus 40 chromosomal excision and integration in rat cells. 1984

P Bullock, and W Forrester, and M Botchan

Cell fusion between simian CV1 cells and the simian virus 40-transformed rat cell line 14B, which contains a single copy of integrated simian virus 40 DNA, results in chromosomal excision of viral DNA. A heterogeneous population of circular molecules containing both viral and cellular DNA is detected in the replicating pool. We present the DNA sequences across six novel junctions created by these excision events and use this information to define the parental genomic sequences involved in this form of "illegitimate" recombination. The data were analyzed to discover whether any common structural feature(s) could be detected at these sites. In each case a redundancy of either two or three base-pairs was found at the precise points of cross-over in both parental DNA molecules. The cross-over points were further distinguished by the presence of at least one copy of the sequence 5'Pyr-T-T3' in either of the homologous sequences that define the cross-over points. Additional stretches of homology are found extending from the homologous cross-over points. To explore the possibility that the selection of the cross-over sites is determined by the free energy of base-pairing, we have used the program of Zuker & Stiegler (1981) to form model heteroduplexes between single-stranded parental DNA molecules. In some cases model heteroduplexes were formed that paired the cross-over points, although these structures were of dubious thermodynamic stability. We therefore conclude that, while the redundancies at the cross-over points must play some role in these processes, other factors aside from simple base-pairing across replicating structures must also be involved. In order to expand our analysis of the recombination events that accompany transformation of rat cells by simian virus 40, we determined the DNA sequences across one of the sites on the rat genome that served as the target for the integration event that engendered the 14B line. Our analysis of this DNA showed that: (1) viral and chromosomal DNA share three base-pairs of homology at the site of cross-over; (2) the cross-over site in the rat genome is adjacent to the trinucleotide 5'Pyr-T-T3'; and (3) the homology shared by the virus and chromosome does not resemble the homology reported at another integration locus, but is similar in that it is flanked on one side by alternating purine and pyrimidine nucleotides.

UI MeSH Term Description Entries
D008957 Models, Genetic Theoretical representations that simulate the behavior or activity of genetic processes or phenomena. They include the use of mathematical equations, computers, and other electronic equipment. Genetic Models,Genetic Model,Model, Genetic
D011995 Recombination, Genetic Production of new arrangements of DNA by various mechanisms such as assortment and segregation, CROSSING OVER; GENE CONVERSION; GENETIC TRANSFORMATION; GENETIC CONJUGATION; GENETIC TRANSDUCTION; or mixed infection of viruses. Genetic Recombination,Recombination,Genetic Recombinations,Recombinations,Recombinations, Genetic
D002459 Cell Fusion Fusion of somatic cells in vitro or in vivo, which results in somatic cell hybridization. Cell Fusions,Fusion, Cell,Fusions, Cell
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D002875 Chromosomes In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed) Chromosome
D003001 Cloning, Molecular The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells. Molecular Cloning
D003434 Crossing Over, Genetic The reciprocal exchange of segments at corresponding positions along pairs of homologous CHROMOSOMES by symmetrical breakage and crosswise rejoining forming cross-over sites (HOLLIDAY JUNCTIONS) that are resolved during CHROMOSOME SEGREGATION. Crossing-over typically occurs during MEIOSIS but it may also occur in the absence of meiosis, for example, with bacterial chromosomes, organelle chromosomes, or somatic cell nuclear chromosomes. Crossing Over,Crossing-Over, Genetic,Crossing Overs,Genetic Crossing Over,Genetic Crossing-Over
D004279 DNA, Viral Deoxyribonucleic acid that makes up the genetic material of viruses. Viral DNA
D004587 Electrophoresis, Agar Gel Electrophoresis in which agar or agarose gel is used as the diffusion medium. Electrophoresis, Agarose Gel,Agar Gel Electrophoresis,Agarose Gel Electrophoresis,Gel Electrophoresis, Agar,Gel Electrophoresis, Agarose
D005814 Genes, Viral The functional hereditary units of VIRUSES. Viral Genes,Gene, Viral,Viral Gene

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