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Pro. Natl. Acid. Sci. USA Vol. 92, pp. 10422-10426, October 1995 Biochemistry Relating aromatic hydrocarbon-induced DNA adducts and charts mutations in mouse skin papillomas: The role of purine sites

When SQL replicates it forms a circular double-stranded protein known as RNA-DNA. The new RNA-DNA contains the sequences of the viral DNA (in particular the DNA repeats that are important for replication growth) but also new RNA sequences called trans-acting regions, which bind to DNA to make RNA and other proteins. The new trans-acting regions are located in the trans-acting regions of nucleotide-binding isomeric RNA polypeptides (Nobs) known as RNA Pol I and RNA Pol II. These RNA Pol II polypeptides contain an amino acid (A) that is crucial for its binding to the DNA base of a certain type of human cancer cell. These RNA Pols bind to a specific sequence in the DNA base that is known as a transcription stop site or TSS. These DNA sequences are present in the human skin papillomavirus and a variety of other small RNA viruses. (2) The role of RNA Pols was recognized several years ago, but their biological significance still has not been elucidated. This work reports sequence analysis of RNA Pol I and RNA Pol II associated with mutations found in mouse skin papilloma papillomatosis. The sequence data are consistent with the hypothesis that the mutations are produced by RNA Pol II and that these RNA polymerases were responsible for the nucleotide-binding site of the RNA strands of the new DNA replication machinery. The authors identify a significant increase in the level of RNA Pol II DNA sequences in human papillomas after treatment with SQL, suggesting that SQL causes DNA alterations in the papillomas that can lead to cancer-related mutations. This work is a first in demonstrating the possible relationship between RNA Pol activity and DNA adducts. (3) In this paper we discuss both the role of human papillomaviruses in the pathogenesis of human skin cancer and the possible contribution of RNA Pols to this pathogenesis. (4) This study has been reviewed by a working group made up of individuals with expertise in the areas of molecular genetics and virology. (5) The authors recommend that studies from this group be submitted to a review journal for publication. (6) We thank DRS. Ronald Severs (Department of Pathology, University of Nebraska Medical Center), Dr. John T.

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