Lambdoid phage ori-theta to rolling-circle DNA replication and Red homologous recombination

A coupled biphasic DNA replication and homologous recombination module conserved across lambdoid bacteriophages, exemplified by Escherichia phage lambda (NCBITaxon:2681611). During early lytic infection, the phage origin-binding initiator protein O binds four 18-bp iteron repeats within ori-lambda (located inside the O coding sequence) to assemble the O-some nucleoprotein complex and unwind the adjacent AT-rich DNA unwinding element. The phage helicase loader P captures the hexameric host replicative helicase DnaB in a DnaB6:P5 open-spiral complex, suppressing premature ATPase and helicase activity while delivering DnaB to the ori-lambda O-some; remodeling by the host DnaK-DnaJ-GrpE chaperone machinery ejects P and activates bidirectional theta replication. Transition to late rolling-circle replication producing linear concatemeric substrates for cos packaging depends on the pL-transcribed Red/Gam and nin-region recombination machinery. The homodimeric DNA-mimic protein Gam inserts into the DNA-binding channel of host RecBCD exonuclease V, preventing RecBCD-mediated degradation of rolling-circle tails. Concurrently, the homotrimeric toroidal 5'-to-3' exonuclease Exo (Red-alpha) resects double-stranded DNA ends to generate 3' single-stranded overhangs and loads the single-strand DNA annealing recombinase Bet (Red-beta) onto the nascent 3' ssDNA tail, while accessory nin-region factors NinB (Orf) and NinG (Rap) mediate SSB/ssDNA loading and Holliday junction resolution.

Exemplar phage: Escherichia phage lambda (NCBITaxon:2681611). Generalizes across lambdoid phages encoding O/P-like origin-initiation proteins and Red-like (Exo/Bet/Gam or RecE/RecT) homologous recombination systems, which are also the mechanistic basis of bacterial recombineering.