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GENES & DEVELOPMENT 21:2461-2472, 2007
©2007 by Cold Spring Harbor Laboratory Press; ISSN 0890-9369/ $5.00
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Cro’s role in the CI–Cro bistable switch is critical for {lambda}’s transition from lysogeny to lytic development

Rachel A. Schubert1, Ian B. Dodd1, J. Barry Egan, and Keith E. Shearwin2

Molecular and Biomedical Sciences (Biochemistry), University of Adelaide, Adelaide, SA 5005, Australia

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 PRM promoter for CI has remained unclear. To address this, we created binding site mutations that strongly impaired Cro repression of PRM with only minimal effects on CI regulation of PRM. 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 PRM 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.

[Keywords: Bistability; epigenetic; bacteriophage {lambda}; genetic switch; Cro; transcriptional control]

Received June 19, 2007; revised version accepted August 7, 2007.

1 These authors contributed equally to this work.

2 Corresponding author.

E-MAIL keith.shearwin{at}adelaide.edu.au; FAX 61-8-8303-4362.

Supplemental material is available at http://www.genesdev.org.

Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1584907


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 Proc. Natl. Acad. Sci. USAHome page
L. M. Anderson and H. Yang
DNA looping can enhance lysogenic CI transcription in phage lambda
PNAS, April 15, 2008; 105(15): 5827 - 5832.
[Abstract] [Full Text] [PDF]


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