The bacteriophage T4 homologous recombination system: mechanism, applications, conservation, and environmental significance.

Abstract

The homologous recombination (HR) system of bacteriophage T4 plays critical, direct roles in the replication and repair of the phage genome. This review covers the classic, UvsX-dependent HR pathway in T4, focusing on recent findings on the mechanisms of central HR proteins UvsX, UvsY, and Gp32, plus the key helicase and nuclease enzymes that affect HR and promote its coupling to T4 recombination-dependent replication and repair processes. The T4 HR pathways are paradigmatic, since they are highly conserved in all orders of viral and cellular life. Therefore, the study of T4 recombination is highly relevant to biomedicine and to environmental microbiology. At the same time, the tractability of the T4 recombination system for biochemical studies has led to the development of novel, isothermal DNA amplification technologies based on the activities of UvsX, UvsY, and Gp32, which are discussed herein. Globally, the recent revolution in metagenomics has demonstrated that T4-like phages, most encoding the genes and proteins of the T4 HR system, are abundant and widespread in the environment, where they play important roles in the dynamics of diverse microbiomes, from the earth's oceans to the animal gut. Accordingly, we discuss the conservation of T4 HR genes in representatives of T4-like jumbo phages and cyanophages. As a paradigm for HR in diverse organisms, as a source of novel technologies, and as a window on the importance of bacteriophages in the environment, the T4 HR system continues to provide new insights and reagents for a better understanding of life on earth.