title: Cro's role in the CI Cro bistable switch is critical for {lambda}'s transition from lysogeny to lytic development.
abstract: CI represses cro; Cro represses cI. This double negative feedback loop is the core of the classical CI-Cro epigenetic switch of bacteriophage lambda. Despite the classical status of this switch, the role in lambda development of Cro repression of the P(RM) promoter for CI has remained unclear. To address this, we created binding site mutations that strongly impaired Cro repression of P(RM) with only minimal effects on CI regulation of P(RM). These mutations had little impact on lambda development after infection but strongly inhibited the transition from lysogeny to the lytic pathway. We demonstrate that following inactivation of CI by ultraviolet treatment of lysogens, repression of P(RM) by Cro is needed to prevent synthesis of new CI that would otherwise significantly impede lytic development. Thus a bistable CI-Cro circuit reinforces the commitment to a developmental transition.
authors.affiliation: Molecular and Biomedical Sciences (Biochemistry), University of Adelaide, Adelaide, SA 5005, Australia.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Schubert
authors.forename: Ian B
authors.initials: IB
authors.lastname: Dodd
authors.forename: J Barry
authors.initials: JB
authors.lastname: Egan
authors.forename: Keith E
authors.initials: KE
authors.lastname: Shearwin
mesh_terms: D010582:Bacteriophage lambda / Q000235:genetics / Q000254:growth & development*; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects; D015967:Gene Expression Regulation, Viral; D008242:Lysogeny / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics; D039002:Prophages / Q000235:genetics / Q000502:physiology; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects; D054334:Viral Regulatory and Accessory Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects; D014775:Virus Activation / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D054334:Viral Regulatory and Accessory Proteins; C016649:phage repressor proteins