The DNA of the tumor virus, SV40, exists in virus particles in association with histones of cellular origin. It can be released as a deoxyribonucleoprotein complex from virions and is quite likely released in this form upon infection. Viral DNA can be recovered from the nuclei of infected cells in a similar complex. Research is proposed to characterize the type and amount of histones and other proteins associated with different regions of the DNA in the genome of SV40 an SV40 variants which contain host cell information. It is expected that these studies will provide insight into the processes of DNA packaging and uncoating which are poorly understood aspects of the biology of SV40. In addition, it is hoped that the nucleoprotein structures to be studied will prove to be a good model system for the study of cellular chromatin, enabling us to investigate the role of the organization of proteins on DNA in replication and transcription. Experiments are proposed to stabilize viral nucleoprotein by introducing reversible chemical cross-links. These cross-linked structures will then be digested with restriction endonucleases, the protein-DNA fragments recovered, the cross-links cleaved, and the DNA and protein components analyzed electrophoretically. Once the procedures have been developed to characterize wild type SV40 nucleoproteins, analysis will be extended to SV40 variants which are presently available giving special consideration to variants containing cellular unique and repetitive sequences. A procedure is outlined to use enzymatic methods to obtain additional SV40 variants containing cellular information from diverse regions of the genome. Such methods can eventually be adapted to generate cloned segments of DNA of known function.