There are many known examples of exclusion of bacteriophages by resident plasmids and prophages but the mechanisms underlying these exclusions are not known. Experiments are proposed to study three exclusions: the exclusion of T4 by the lit gene product of the cryptic DNA element, e14; the exclusion of T4 polynucleotide kinase and RNA ligase deficient mutants by the prr gene product of another cryptic DNA element; and the exclusions promoted by the rex gene products of the prophage. We shall use gene fusions to determine the mechanisms of the local and global inhibition of gene expression promoted by the interaction between the Lit protein and a short sequence within the major head protein gene of T4. To explain the local inhibition the gol region may become a transcriptional terminator or target the RNA for degradation in the presence of Lit protein. The global inhibition may be due to the cleavage of an RNA or phosphorylation of a protein which is part of the translation apparatus. Alternatively, it may be due to generation of a small RNA or other inhibitor of translation. Other experiments will be directed toward determining the role of the prr and stp gene products as well as other auxiliary factors in the cleavage of host tRNA, and in searching for introns removed by the polynucleotide kinase and RNA ligase. Finally, a system we've devised for inducing the rex inhibitions in the absence of phage superinfection will by used to find the primary target of the rex gene products leading to the global inhibition of cellular functions.
