The main objective of our research is to understand at the molecular level the DNA: protein and protein:protein interactions which underlie the basic genetic process of DNA replication; and which make possible its careful regulation and control during the cell cycle. We are concentrating on accessible biological materials which provide model systems where meaningful biochemistry can be done. Thus, to study the mechanism by which deoxyribonucleotide triphosphates are polymerized into two daughter, DNA double-helices at the replication fork, we have chosen the proteins of the T4 bacteriophage replication apparatus for detailed analysis. Here we have already isolated 6 essential T4 replication proteins in purified active form. The function of 4 of these proteins is as yet unknown. For extending these studies to eukaryotes (and particularly to study how higher cells communicate between nucleus and cytoplasm, and how they distinguish the sections of DNA which have already replicated in a given S-phase from the sections of DNA which remain to be replicated (replication control)), we have begun work with the perfectly synchronized eukaryote, Physarum polycephalum (acellular slime mold). Here we propose to develop new methods which will allow us to study the movement of specific proteins in and out of the cell nucleus as a function of the cell cycle.