Role of host factors in bacteriophage φ29 DNA replication.

Abstract During the course of evolution, viruses have learned to take advantage of the natural resources of their hosts for their own benefit. Due to their small dimension and limited size of genomes, bacteriophages have optimized the exploitation of bacterial host factors to increase the efficiency of DNA replication and hence to produce vast progeny. The Bacillus subtilis phage ϕ29 genome consists of a linear double-stranded DNA molecule that is duplicated by means of a protein-primed mode of DNA replication. Its genome has been shown to be topologically constrained at the size of the bacterial nucleoid and, as to avoid generation of positive supercoiling ahead of the replication forks, the bacterial DNA gyrase is used by the phage. In addition, the B . subtilis actin-like MreB cytoskeleton plays a crucial role in the organization of ϕ29 DNA replication machinery in peripheral helix-like structures. Thus, in the absence of an intact MreB cytoskeleton, ϕ29 DNA replication is severely impaired. Importantly, MreB interacts directly with the phage membrane protein p16.7, responsible for attaching ϕ29 DNA at the cell membrane. Moreover, the ϕ29-encoded protein p56 inhibits host uracil–DNA glycosylase activity and has been proposed to be a defense mechanism developed by the phage to prevent the action of the base excision repair pathway if uracil residues arise in replicative intermediates. All of them constitute incoming examples on how viruses have profited from the cellular machinery of their hosts.