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A Genetic Switch : Phage Lambda Revisited :  Phage Lambda Revisited - Mark Ptashne

A Genetic Switch : Phage Lambda Revisited

Phage Lambda Revisited

Paperback Published: April 2004
ISBN: 9780879697167
Number Of Pages: 154

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The first edition of Mark Ptashne's 1986 book describing the principles of gene regulation in phage lambda became a classic in both content and form, setting a standard of clarity and precise prose that has rarely been bettered. This edition is a reprint of the original text together with a new chapter updating the story to 2004. Among the striking new developments are recent findings on long-range interactions between proteins bound to widely separated sites on the phage genome, and a detailed description of how gene activation works.

Ptashne's clear and concise articulation of the essential scientific and experimental issues makes the book an ideal introductory text for the increasing number of interdisciplinary scientists moving into systems biology. More importantly, the detailed studies (summarized in these chapters) that relate properties of the molecular components to the function of the switch establish a high standard for the systems biology of more complex organisms. Science The clarity and care of 'A Genetic Switch' and its organization is a paradigm for communicating the structure and behavior of complex regulatory systems such as lambda. Periodic update of a book like this is important as a reminder of the level of our understanding of a system, in this case lambda, and of how we achieved that understanding. 'A Genetic Switch' is wonderful for what it is-a beautiful, concise (only 154 pages) exposition of the major molecular processes involved in lambda's lysis-lysogeny and induction decisions...The 3rd edition of 'A Genetic Switch' prompts us to remember the power of this under-utilized model system in discovering general principles of cellular function and behavior. Switch back!" Current Biology I enjoyed the book and have no major quibbles. The author has a talent for simplifying (but not oversimplifying) complicated ideas, he describes the theory and its experimental basis in a straightforward and plainspoken way, and he illustrates his points with drawings that contain just the right amount of detail. Connoisseurs will appreciate the new chapter on recent developments, in which some parts of the original picture are redrawn and others filled in... I strongly recommend the new edition of A Genetic Switch to students of molecular biology from the advanced undergraduate level up. The author and publisher are to be commended for supplying this volume at such a reasonable price. The Quarterly Review of Biology

Preface to the Third Editionp. xi
Preface to the First Editionp. xiii
Introductionp. 1
The Master Elements of Controlp. 11
Components of the Switchp. 14
DNAp. 14
RNA Polymerasep. 15
The Repressorp. 16
Crop. 17
The Action of Repressor and Crop. 18
Negative Controlp. 18
Positive Controlp. 18
Cooperativity of Repressor Bindingp. 20
Induction--Flipping the Switchp. 22
Cooperativity--Switch Stability and Sensitivityp. 26
The Effect of Autoregulationp. 28
Other Casesp. 28
Protein-DNA Interactions and Gene Controlp. 31
The Operatorp. 31
Repressorp. 34
Crop. 37
Amino Acid-Base Pair Interactionsp. 39
The Promoterp. 43
Gene Controlp. 44
Control Circuits--Setting the Switchp. 47
A Brief Overview of [lambda] Growthp. 48
The Genetic Mapp. 48
Circularizationp. 49
Gene Expressionp. 50
Integrationp. 51
Control of Transcriptionp. 52
Very Earlyp. 52
Earlyp. 52
Late Lyticp. 53
Late Lysogenicp. 55
The Decisionp. 56
Control of Integration and Excisionp. 57
Establishing Lysogenyp. 58
Lytic Growthp. 58
Inductionp. 58
Other Phagesp. 60
The SOS Responsep. 60
[lambda] Pathways and Cell Developmentp. 62
Regulatory Genesp. 62
Switchesp. 63
Patterns of Gene Expressionp. 64
How Do We Know--the Key Experimentsp. 67
The Repressor Ideap. 67
Clear and Virulent Mutantsp. 67
Observationsp. 67
Explanationp. 68
Immunity and Heteroimmunityp. 69
Observationsp. 69
Explanationp. 70
Asymmetry in Bacterial Matingp. 70
Observationsp. 70
Explanationp. 71
The Repressor Problem in the Early 1960sp. 71
Repressor Isolation and DNA Bindingp. 72
Making More Repressorp. 74
The Claims of Chapters One and Twop. 76
The repressor is composed of two globular domains held together by a linker of some 40 amino acidsp. 76
The repressor dimerizes, largely through interaction between its carboxyl domainsp. 76
A repressor dimer binds, through its amino domains, to a 17 base pair operator sitep. 78
A single operator site binds one dimer of repressorp. 78
Dimers form before DNA bindingp. 80
The amino domains contact DNAp. 82
There are three 17 base pair repressor binding sites in the right operator. At each site repressor and Cro bind along the same face of the helixp. 84
Chemical probesp. 84
Operator mutationsp. 85
Binding to supercoiled and linear DNAp. 85
Repressor binds to three sites in O[subscript R] with alternate pairwise cooperativity. The cooperativity is mediated by interactions between carboxyl domains of adjacent dimersp. 86
In a lysogen repressor is typically bound to O[subscript R]1 and O[subscript R]2. The bound repressors turn off rightward transcription of cro and stimulate leftward transcription of cl. At higher concentrations, repressor binds to O[subscript R]3 to turn off transcription of clp. 87
Cro binds first to O[subscript R]3, then to O[subscript R]1 and O[subscript R]2, thereby first turning off P[subscript RM], then P[subscript R]p. 92
Some background about Crop. 92
Cro in vivop. 93
Cro in vitrop. 94
RecA cleaves repressor to trigger inductionp. 94
When Cro is bound at O[subscript R]3 the switch is thrownp. 95
Repressor and Cro bind to the operator as shown in Figures 2.6, 2.8, 2.10, and 2.11p. 95
Crystallographyp. 95
The "helix swap" experimentp. 96
Specific amino acid-base pair contactsp. 98
The role of the arm of [lambda] repressorp. 99
Repressor activates transcription of cl by binding to O[subscript R]2 and contacting polymerase with its amino domainp. 99
Positive control mutantsp. 99
Positive control in vitrop. 102
Conclusionp. 103
2004: New Developmentsp. 109
Long-range Cooperativity and Repression of P[subscript RM]p. 109
An Octamer of Repressor Binds O[subscript R] and O[subscript L]p. 110
Autonegative Regulation of Repressor Synthesisp. 112
How Do We Knowp. 113
Long-range Interactions and Repression of P[subscript R]p. 113
Long-range Interactions and Repression of P[subscript RM]p. 114
Activation and Repression of P[subscript RM]p. 114
Repressor Structurep. 115
Positive Control (Activation of Transcription)p. 122
Polymerase and Promoterp. 122
The Mechanism of Activationp. 123
How Do We Knowp. 123
Activating Region Variantsp. 123
A Suppressor of a pc Mutantp. 125
Crystallographyp. 125
Activator Bypassp. 125
Changing Activating Regions and Target Contextp. 127
The Structure of the Repressor Monomer and the Mechanism of Repressor Cleavagep. 131
How Do We Knowp. 132
Evolving the Switchp. 133
Changing the Affinities of Sites in O[subscript R] for Repressorp. 133
Eliminating Positive Controlp. 134
Eliminating Cooperativity between DNA-binding Dimersp. 134
CII and the Decisionp. 136
Indexp. 151
Table of Contents provided by Rittenhouse. All Rights Reserved.

ISBN: 9780879697167
ISBN-10: 0879697164
Series: Ptashne, a Genetic Switch
Audience: Tertiary; University or College
Format: Paperback
Language: English
Number Of Pages: 154
Published: April 2004
Publisher: Cold Spring Harbor Laboratory Press,U.S.
Country of Publication: US
Dimensions (cm): 22.2 x 16.5  x 1.3
Weight (kg): 0.57
Edition Number: 3
Edition Type: Revised