The objective of this research is to determine the exact relationship between the structure of chromatin and replication of DNA. This relationship is fundamental to understanding the molecular basis of mammalian cell growth, tumor virus replication, integration of viral DNA into cellular DNA, and transformation of normal cells into cancer cells. The selection of the SV40 genome as our primary experimental system will allow us to analyze in detail a pure, homogeneous, undamaged population of chromatin. This viral genome is well characterized and can be isolated as intact replicating molecules which will permit us to study the disassembly and reassembly of chromatin during replication, as well as the role of chromatin structure in the process of discontinuous DNA synthesis.