PHAGE-EXCLUSION ENZYMES - A BONANZA OF BIOCHEMICAL AND CELL BIOLOGY REAGENTS

Many parasitic DNA elements including prophages and plasmids synthesiz e proteins that kill the cell after infection by other phages, thereby blocking the multiplication of the infecting phages and their spread to other nearby cells. The only known function of these proteins is to exclude the infecting phage, and therefore to protect their hosts, an d thereby the DNA elements themselves, against phage contagion. Many o f these exclusions have been studied extensively and some have long be en used in molecular genetics, but their molecular basis was unknown. The most famous of the phage exclusions are those caused by the Rex pr oteins of lambda prophage. The Rex exclusions are still not completely understood, but recent evidence has begun to lead to more specific mo dels for their action. One of the Rex proteins, RexA, may be activated by a DNA-protein complex, perhaps a recombination or replication inte rmediate, produced after phage infection. In the activated state, RexA may activate RexB, which has been proposed to be a membrane ion chann el that allows the passage of monovalent cations, destroying the cellu lar membrane potential, and killing the cell. We now understand two ot her phage exclusions at the molecular level which use strategies that are remarkably similar to each other. The parasitic DNA elements respo nsible for. the exclusions both constitutively synthesize enzymes that are inactive as synthesized by the DNA element but are activated afte r phage infection by a short peptide determinant encoded by the infect ing phage. In the activated state, the enzymes cleave evolutionarily c onserved components of the translation apparatus, in one case EF-Tu, a nd in the other case tRNA(Lys). Translation is blocked and development of the phage is arrested. A myriad of different phage-exclusion syste ms are known to exist and many of these may also be specific for highl y conserved cellular components, furnishing generally useful enzymes f or biochemical and biomedical research.