The lysis-lysogeny decision of bacteriophage 933W: A 933W repressor-mediated long-distance loop has no role in regulating 933W P_RM activity

Our data show that unlike bacteriophage λ, repressor bound at O_L of bacteriophage 933W has no role in regulation of 933W repressor occupancy of 933W O_R3 or the transcriptional activity of 933W P_RM. This finding suggests that a cooperative long-range loop between repressor tetramers bound at O_R andO_L does not form in bacteriophage 933W. Nonetheless, 933W forms lysogens, and 933W prophage display a threshold response to UV induction similar to related lambdoid phages. Hence, the long-range loop thought to be important for constructing a threshold response in lambdoid bacteriophages is dispensable. The lack of a loop requires bacteriophage 933W to use a novel strategy in regulating its lysis-lysogeny decisions. As part of this strategy, the difference between the repressor concentrations needed to bind O_R2 and activate 933W P_RM transcription or bind O_R3 and repress transcription from P_RM is <2-fold. Consequently, P_RM is never fully activated, reaching only ~25% of the maximum possible level of repressor-dependent activation before repressormediated repression occurs. The 933W repressor also apparently does not bind cooperatively to the individual sites in O_R andO_L. This scenario explains how, in the absence of DNA looping, bacteriophage 933W displays a threshold effect in response to DNA damage and suggests how 933W lysogens behave as "hair triggers" with spontaneous induction occurring to a greater extent in this phage than in other lambdoid phages.