Two recombination-dependent DNA replication pathways of bacteriophage T4, and their roles in mutagenesis and horizontal gene transfer

Two major pathways of recombination-dependent DNA replication, "join-copy" and "join-cut-copy," can be distinguished in phage T4: join-copy requires o nly early and middle genes, but two late proteins, endonuclease VII and ter minase, are uniquely important in the join-cut-copy pathway. In wild-type T 4, timing of these pathways is integrated with the developmental program an d related to transcription and packaging of DNA. In primase mutants, which are defective in origin-dependent lagging-strand DNA synthesis, the late pa thway can bypass the lack of primers for lagging-strand DNA synthesis, The exquisitely regulated synthesis of endo VII, and of two proteins from its g ene, explains the delay of recombination-dependent DNA replication in prima se las well as topoisomerase) mutants, and the temperature-dependence of th e delay. Other proteins (e.g., the single-stranded DNA binding protein and the products of genes 46 and 47) are important in all recombination pathway s, but they interact differently with other proteins in different pathways. These homologous recombination pathways contribute to evolution because th ey facilitate acquisition of any foreign DNA with limited sequence homology during horizontal gene transfer, without requiring transposition or site-s pecific recombination functions. Partial heteroduplex repair can generate w hat appears to be multiple mutations from a single recombinational intermed iate. The resulting sequence divergence generates barriers to formation of viable recombinants. The multiple sequence changes can also lead to erroneo us estimates in phylogenetic analyses.