NDLI: DNA looping provides stability and robustness to the bacteriophage λ switch

Content Provider	PubMed Central
Author	Morelli, Marco J. Wolde, Pieter Rein Ten Allen, Rosalind J.
Abstract	The bistable gene regulatory switch controlling the transition from lysogeny to lysis in bacteriophage λ presents a unique challenge to quantitative modeling. Despite extensive characterization of this regulatory network, the origin of the extreme stability of the lysogenic state remains unclear. We have constructed a stochastic model for this switch. Using Forward Flux Sampling simulations, we show that this model predicts an extremely low rate of spontaneous prophage induction in a recA mutant, in agreement with experimental observations. In our model, the DNA loop formed by octamerization of CI bound to the O L and O R operator regions is crucial for stability, allowing the lysogenic state to remain stable even when a large fraction of the total CI is depleted by nonspecific binding to genomic DNA. DNA looping also ensures that the switch is robust to mutations in the order of the O R binding sites. Our results suggest that DNA looping can provide a mechanism to maintain a stable lysogenic state in the face of a range of challenges including noisy gene expression, nonspecific DNA binding, and operator site mutations.
Related Links	http://dx.doi.org/10.1073/pnas.0810399106
Ending Page	8106
Page Count	6
Starting Page	8101
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	20
Volume Number	106
Language	English
Publisher	National Academy of Sciences
Publisher Date	2009-05-19
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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Correction for Morelli et al., DNA looping provides stability and robustness to the bacteriophage λ switch

DNA looping provides stability and robustness to the bacteriophage lambda switch

Direct demonstration and quantification of long-range DNA looping by the λ bacteriophage repressor

Multilevel autoregulation of λ repressor protein CI by DNA looping in vitro

THE FORMATION OF λ BACTERIOPHAGE BY λ DNA IN DISRUPTED CELL PREPARATIONS *

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Direct demonstration and quantification of long-range DNA looping by the λ bacteriophage repressor

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DNA looping provides stability and robustness to the bacteriophage λ switch

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Correction for Morelli et al., DNA looping provides stability and robustness to the bacteriophage λ switch

DNA looping provides stability and robustness to the bacteriophage lambda switch

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