Affiliation:
1. Department of Molecular Biology, Vanderbilt University, Nashville, Tennessee 37235;
Abstract
▪ Abstract General recombination is essential for growth of phage T4, because origin initiation of DNA replication is inactivated during development, and recombination-dependent initiation is necessary for continuing DNA replication. The requirement of recombination for T4 growth has apparently been a driving force to acquire and maintain multiple recombination mechanisms. This requirement makes this phage an excellent model to analyze several recombination mechanisms that appear redundant under optimal growth conditions but become essential under other conditions, or at different stages of the developmental program. The most important substrate for wild-type T4 recombination is single-stranded DNA generated by incomplete replication of natural or artificial chromosomal ends, or by nucleolytic degradation from induced breaks, or nicks. Recombination circumvents the further erosion of such ends. There are multiple proteins and multiple pathways to initiate formation of recombinants (by single-strand annealing or by strand invasion) and to convert recombinational intermediates into final recombinants (“cut and paste” or “cut and package”), or to initiate extensive DNA replication by “join-copy” or “join-cut-copy” mechanisms. Most T4 recombination is asymmetrical, favoring the initiation of replication. In wild-type T4 these pathways are integrated with physiological changes of other DNA transactions: mainly replication, transcription, and packaging. DNA replication and packaging enzymes participate in recombination, and recombination intermediates supply substrates for replication and packaging. The replicative recombination pathways are also important for transmission of intron DNA to intronless genomes (“homing”), and are implicated in horizontal transfer of foreign genes during evolution of the T-even phages. When horizontal transfer involves heteroduplex formation and repair, it is intrinsically mutagenic and contributes to generation of species barriers between phages.
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168 articles.
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