Chronology of Becoming a Lysogen
We now examine how an infecting lambda phage eventually shuts down gene activity of all but three of its genes when it lysogenizes a cell. The beginning steps are the same as in a lytic infection: DNA is injected into the cell, and the N and Cro proteins, which are sometimes called the immediate early genes, begin to accumulate. Then the remainder of the proteins synthesized under control of the pL and pR promoters, including CII and CIII, begin to be synthesized. These latter proteins are crucial to the lysogenic response in three ways. First, they are necessary for the initial synthesis of CI; second, they are necessary for adequate synthesis of the phage protein required for integration of phage DNA into the host DNA, the Int protein; and third, they delay or reduce the expression of the Q protein that turns on late protein synthesis.
The CII protein activates transcription from three phage promoters pRE, pI, and pAQ. The CIII protein works with CII somehow to protectCII from the action of proteases within the cell. The sensitivity of CII to proteases and the protection provided by CIII generate a response highly
sensitive to the physiological state of the cell. It is this response that determines whether or not a cell will proceed down the lytic or the lysogenic developmental pathways. The promoter pRE is located to the right of cro and is oriented in the direction opposite to pR. Thus the initial part of the RNA synthesized under control of this promoter is anti-cro messenger and likely reduces Cro protein synthesis. The re-mainder of the messenger encodes repressor protein, the CI gene prod-uct, as well as two other proteins in this operon, RexA and RexB. The pIpromoter lies partly in the xis gene and is just in front of the int gene.The pAQ promoter is located within the Q gene and oriented in the opposite direction. Thus, the pAQ promoter specifies the synthesis of antimessenger that reduces Q protein synthesis until CII is gone.
In infected cells that will become lysogens, repressor soon reaches a level sufficient to bind to the operators that overlap pL and pR. This binding shuts off synthesis of N, Cro, and the other early gene products. Hence, although a little Exo, P, Î³, O, P, and Q have accumulated, their levels are insufficient to sustain growth. Lambda destined to become a lysogen may even undergo several rounds of DNA replication, but then the early genes are shut off and the instability of O prevents further development. The Int protein, which also has been synthesized at high rates under control of pI, participates with a number of host proteins in the integration of one copy of the lambda DNA into the host.
After high levels of lambda repressor have effectively shut off the phage early promoters, four phage promoters can still produce func-tional messenger, pRM, pRE, pI, andpAQ. However as CII and CIII lose activity and are diluted away with cell growth, pRE, pI, and pAQ shut down and leave only the promoter for the maintenance of repressor synthesis, pRM, active. The program of shut-down occurs whether or not lambdahas been successful in integrating itself into the host chromosome. If integration has occurred, then the lambda DNA is replicated by the host machinery upon each synthesis cycle and each daughter cell inherits a copy of the lambda genome and is lysogenic. If integration has not occurred, then lambda is passed to only one daughter and soon is effectively lost by dilution.