The lysis-lysogeny decision by phage Lambda
- Uncommitted. Soon after lambda enters a cell:
- RNAP inititates transcription at PR. Transcription terminates at tR1, resulting in expression of Cro protein.
- RNAP inititates transcription at PL. Transcription terminates at tL1, resulting in expression of N protein.
- N protein prevents termination at tR1 and tL1 allowing expression of cII and cIII proteins.
- Committment. The lysis-lysogeny decision is determined by the accumulation of cII protein.
- Lysogeny. If sufficient cII protein accumulates, cII binds to PRE and activates transcription of cI gene and cII binds to PI and activates transcription of the int gene. Because cII protein is rapidly degraded by a protease encoded by the host hfl gene, accumulation of sufficient cII protein depends upon two factors:
- growth conditions of the host cells (poor growth conditions inhibit Hfl, resulting in a greater accumulation of cII),
- multiplicity of infection (high MOI results in increased [cIII protein] which inhibits proteolysis of cII protein).
- Lysis. If cII protein is degraded, RNAP is unable to initiate transcription from PRE or PI, so transcription continues from PL and PR.
- Execution. Either lysogeny or lysis will result depending upon the accumulation of cII protein during the committment stage.
- activation of cI expression from PRE results in accumulation of cI protein
- expression of int from PI results in accumulation of integrase protein
- cI protein binds to OL and represses N expression ([N protein] rapidly decreases because N is unstable)
- cI protein binds to OR and represses O, P, and Q expression
- cI protein binds to OR and activates its own expression from PRM
- decreased [cII protein] cannot activate cI expression from PRE
- transcription from PR continues to express O, P, and Q proteins
- Q protein prevents termination at tR2 allowing expression of PLate operon
- [Cro protein] increases due to transcription from PR
- Cro protein binds to OR and OL and represses expression of early gene products
Note that a key step in the lysis-lysogeny decisioin is the regulation of cII protein. The following cartoon shows how physiological events modulate cII expression.
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Last modified November 12, 2003