Closed circular DNAs with tandem repeats of a sequence from polyoma virus.

The small size of the genomes of SV-40 and polyoma viruses provide some reason to hope that one or more viral gene products(s) responsible for neoplastic transformation might be identified. However, recent reports that the genomes of SV-40 and polyoma viruses are easily changed, acquiring host sequences or losing viral sequences, suggest that their size may misrepresent their complexity (Yoshiike 1968a,b; Thorne, 1968; Thorne et al., 1968; Aloni et al., 1969; Blackstein et al., 1969; Lavi and Winocur, 1972, 1974; Tai et al., 1972; Yoshiike et al., 1972. Recently, several laboratories have made a great deal of progress in characterizing the structure of the SV-4Q genome, using sequence-specific nucleases (Morrow and Berg, 1972; Mulder and Delius, 1972; Fareed et al., 1972; Danna et al., 1973; Khoury et al., 1973). In this report we demonstrate that multiple infection of cells by polyoma virus permits the accumulation of defective viral genomes. A frequent closed circular DNA molecule which is selected for, and which often predominates in the pool of replicating DNA, has lost or had modified the sequence (5’) GAATTC recognized and cleaved by the R, restriction endonuclease (Hedgpeth et al., 1972). We have characterized one such population of defective molecules, and show that they contain repetitions of a subset of the sequences of the polyoma genome, and are relatively homogeneous.