Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
RNA Biology Laboratory, National Cancer Institute/Frederick Cancer Research and Development Center, Frederick, Maryland, USA.
Mol Microbiol. 2021 Oct;116(4):1044-1063. doi: 10.1111/mmi.14792. Epub 2021 Aug 30.
The CI and Cro repressors of bacteriophage λ create a bistable switch between lysogenic and lytic growth. In λ lysogens, CI repressor expressed from the P promoter blocks expression of the lytic promoters P and P to allow stable maintenance of the lysogenic state. When lysogens are induced, CI repressor is inactivated and Cro repressor is expressed from the lytic P promoter. Cro repressor blocks P transcription and CI repressor synthesis to ensure that the lytic state proceeds. RexA and RexB proteins, like CI, are expressed from the P promoter in λ lysogens; RexB is also expressed from a second promoter, P , embedded in rexA. Here we show that RexA binds CI repressor and assists the transition from lysogenic to lytic growth, using both intact lysogens and defective prophages with reporter genes under the control of the lytic P and P promoters. Once lytic growth begins, if the bistable switch does return to the immune state, RexA expression lessens the probability that it will remain there, thus stabilizing the lytic state and activation of the lytic P and P promoters. RexB modulates the effect of RexA and may also help establish phage DNA replication as lytic growth ensues.
噬菌体 λ 的 CI 和 Cro 阻遏物在溶原性和裂解性生长之间创建了一个双稳态开关。在 λ 溶原菌中,从 P 启动子表达的 CI 阻遏物阻止裂解启动子 P 和 P 的表达,从而允许溶原状态的稳定维持。当溶原菌被诱导时,CI 阻遏物失活,Cro 阻遏物从裂解 P 启动子表达。Cro 阻遏物阻止 P 转录和 CI 阻遏物合成,以确保裂解状态进行。RexA 和 RexB 蛋白与 CI 一样,从 λ 溶原菌的 P 启动子表达;RexB 也从第二个启动子 P 表达,该启动子嵌入在 rexA 中。在这里,我们使用带有报告基因的完整溶原菌和带有报告基因的缺陷原噬菌体表明,RexA 结合 CI 阻遏物并协助从溶原性到裂解性生长的转变,这些报告基因受裂解 P 和 P 启动子的控制。一旦开始裂解性生长,如果双稳态开关确实返回免疫状态,RexA 的表达会降低其保持在该状态的可能性,从而稳定裂解状态并激活裂解 P 和 P 启动子。RexB 调节 RexA 的作用,并且在裂解性生长开始时也可能有助于建立噬菌体 DNA 复制。