The experimental approaches to be used are directed towards understanding the regulation of adenovirus replication and cell transformation. Five major projects will be developed: 1) Large scale purification of the adenovirus-specific DNA-binding product, identified as the "gene 125 protein"; 2) Investigate further the role of the DNA-binding protein in transformation and viral DNA integration; 3) Study the regulation of transcription of viral mRNAs in H5ts125-transformed cells containing different amounts and different regions of the viral genome; 4) Identify and characterize the viral gene product defective in H5ts149; and 5) Attempt to determine why relatively few genes are mutated by the mutagenic procedures presently used to obtain adenovirus mutants. BIBLIOGRAPHIC REFERENCES: Carter, T.H. and Ginsberg, H.S. Viral Transcription in LB Cells Infected by Temperature-sensitive "Early" Mutants of Type 5 Adenovirus. J. Virol., 1976, 18:156-166. Straus, S.E., Ginsberg, H.S., and Rose, J.A. DNA-minus Temperature-sensitive Mutants of Adenovirus Type 5 Help Adenovirus-associated Virus Replication, J. Virol., 1976, 17:140-148.