Abstract:
:Complex gene regulatory circuits contain many interacting components. In principle, all of these components and interactions may be essential to the function of the circuit. Alternatively, some of them may be refinements to a simpler version of the circuit that improve its fitness. In this work, we have tested whether a particular property of a critical regulatory protein, CI, is essential to the behavior of the phage lambda regulatory circuit. In the lysogenic state, CI represses the expression of the lytic genes, allowing a stable lysogenic state, by binding cooperatively to six operators. A mutant phage lacking cooperativity because of a change in cI could not form stable lysogens; however, this defect could be suppressed by the addition of mutations that altered two cis-acting sites but did not restore cooperativity. The resulting triple mutant was able to grow lytically, form stable single lysogens, and switch to lytic growth upon prophage induction, showing a threshold response in switching similar to that of wild-type lambda. We conclude that cooperative DNA binding by CI is not essential for these properties of the lambda circuitry, provided that suppressors increase the level of CI. Unlike wild-type lysogens, mutant lysogens were somewhat unstable under certain growth conditions. We surmise that cooperativity is a refinement to a more basic circuit, and that it affords increased stability to the lysogenic state in response to environmental variations.
journal_name
Proc Natl Acad Sci U S Aauthors
Babić AC,Little JWdoi
10.1073/pnas.0602223104subject
Has Abstractpub_date
2007-11-06 00:00:00pages
17741-6issue
45eissn
0027-8424issn
1091-6490pii
0602223104journal_volume
104pub_type
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