Editing Lambda phage

{{short description|Bacteriophage that infects Escherichia coli}}
{{context|date=September 2013}}

{{virusbox
| name = Lambda phage
| image_caption =  Electron micrograph of a virus particle of lambda phage
| image = Lambda EM.jpg
| parent = Lambdavirus
| species = Lambdavirus lambda
}}
[[File:Bacteriophage Lambda Structure.jpg|thumb|Bacteriophage Lambda Structure at Atomic Resolution<ref>{{Citation |last=Victor Padilla-Sanchez |title=Bacteriophage Lambda Structure at Atomic Resolution |date=2024-11-25 |url=https://zenodo.org/doi/10.5281/zenodo.14219202 |access-date=2024-11-25 |doi=10.5281/zenodo.14219202}}</ref>]]
'''Lambda phage''' ('''coliphage λ''', scientific name '''''Lambdavirus lambda''''') is a bacterial virus, or [[bacteriophage]], that infects the bacterial species ''[[Escherichia coli]]'' (''E. coli'').  It was discovered by [[Esther Lederberg]] in 1950.<ref>{{cite journal | vauthors = Lederberg E | title = Lysogenicity in ''Escherichia coli'' strain K-12 | journal = Microbial Genetics Bulletin | volume = 1 | pages = 5–8 | date = January 1950 }}; followed by {{cite journal | vauthors = Lederberg EM, Lederberg J | title = Genetic Studies of Lysogenicity in Escherichia Coli | journal = Genetics | volume = 38 | issue = 1 | pages = 51–64 | date = January 1953 | pmid = 17247421 | pmc = 1209586 | doi = 10.1093/genetics/38.1.51 }}</ref> The wild type of this virus has a [[Temperate (virology)|temperate]] life cycle that allows it to either reside within the [[genome]] of its host through [[lysogeny]] or enter into a [[lytic]] phase, during which it kills and lyses the cell to produce offspring. Lambda strains, mutated at specific sites, are unable to lysogenize cells; instead, they grow and enter the lytic cycle after superinfecting an already lysogenized cell.<ref>{{cite book| vauthors =  Griffiths A, Miller J, Suzuki D, Lewontin R, Gelbart W |title=An Introduction to Genetic Analysis|date=2000|publisher=W. H. Freeman|location=New York|isbn=978-0-7167-3520-5|edition=7th|url=https://www.ncbi.nlm.nih.gov/books/NBK21856/|access-date=19 May 2017}}</ref>

The phage particle consists of a head (also known as a [[capsid]]),<ref>{{cite journal | vauthors = Wang C, Zeng J, Wang J | title = Structural basis of bacteriophage lambda capsid maturation | journal = Structure | volume = 30 | issue = 4 | pages = 637–645.e3 | date = April 2022 | pmid = 35026161 | doi = 10.1016/j.str.2021.12.009 | s2cid = 245933331 | doi-access = free }}</ref> a tail, and tail fibers (see image of virus below). The head contains the phage's double-strand linear [[DNA]] genome. During infections, the phage particle recognizes and binds to its host, ''E. coli'', causing DNA in the head of the phage to be ejected through the tail into the cytoplasm of the bacterial cell. Usually, a "[[lytic cycle]]" ensues, where the lambda DNA is replicated and new phage particles are produced within the cell. This is followed by cell [[lysis]], releasing the cell contents, including virions that have been assembled, into the environment. However, under certain conditions, the phage DNA may integrate itself into the host cell chromosome in the [[lysogenic]] pathway. In this state, the λ DNA is called a [[prophage]] and stays resident within the host's [[genome]] without apparent harm to the host. The host is  termed a [[lysogen]] when a prophage is present. This prophage may enter the lytic cycle when the lysogen enters a stressed condition.

==Anatomy==
[[File:Phage lambda virion.svg|thumb|250px|alt=The bacteriophage lambda virion | Bacteriophage lambda virion (schematic). Protein names and their copy numbers in the virion particle are shown. The presence of the L and M proteins in the virion is still unclear.<ref name="Raja_lambda">{{cite journal | vauthors = Rajagopala SV, Casjens S, Uetz P | title = The protein interaction map of bacteriophage lambda | journal = BMC Microbiology | volume = 11 | pages = 213 | date = September 2011 | pmid = 21943085 | pmc = 3224144 | doi = 10.1186/1471-2180-11-213 | doi-access = free }}</ref>]]

The virus particle consists of a head and a tail that can have tail fibers. The whole particle consists of 12–14 different proteins with more than 1000 protein molecules total and one DNA molecule located in the phage head. However, it is still not entirely clear whether the L and M proteins are part of the virion.<ref name="Raja_lambda" /> All characterized [[lambdoid phage]]s possess an N protein-mediated transcription antitermination mechanism, with the exception of phage HK022.<ref name="src3">{{cite journal | vauthors = Casjens SR, Hendrix RW | title = Bacteriophage lambda: Early pioneer and still relevant | journal = Virology | volume = 479-480 | pages = 310–330 | date = May 2015 | pmid = 25742714 | pmc = 4424060 | doi = 10.1016/j.virol.2015.02.010 }}</ref>
[[File:LambdaPhage Genome Linear.svg|thumb|498 px|center|Linear layout of lambda phage genome with major operons, promoter regions and capsid coding genes.<ref name="Raja_lambda"/>]]

The [[genome]] contains 48,502<ref>{{cite web | url=https://www.ncbi.nlm.nih.gov/nuccore/215104 | title=Escherichia phage Lambda, complete genome | date=6 January 2020 }}</ref> base pairs of double-stranded, linear DNA, with 12-base single-strand segments at both 5' ends.<ref name="CampbellPhage">{{cite book | vauthors = Campbell AM | chapter = Bacteriophages | veditors = Neidhardt FC, Curtiss R | date = 1996 | title = ''Escherichia coli'' and ''Salmonella typhimurium'': Cellular and Molecular Biology | publisher = ASM Press | location = Washington, DC | oclc = 1156862867 }}</ref> These two single-stranded segments are the "sticky ends" of what is called the ''cos'' site. The ''cos'' site circularizes the DNA in the host cytoplasm. In its circular form, the phage genome, therefore, is 48,502 base pairs in length.<ref name="CampbellPhage"/>  The lambda genome can be inserted into the '' E. coli'' chromosome and is then called a prophage. See section below for details.
{{clear}}

The tail of lambda phages is made of at least 6 proteins (H, J, U, V, Stf, Tfa) and requires 7 more for assembly (I, K, L, M, Z, G/T). This assembly process begins with protein J, which then recruits proteins I, L, K, and G/T to add protein H. Once G and G/T leave the complex, protein V can assemble onto the J/H scaffold. Then, protein U is added to the head-proximal end of the tail. Protein Z is able to connect the tail to the head. Protein H is cleaved due to the actions of proteins U and Z.<ref name="Raja_lambda" />

== Life cycle ==
=== Infection ===
[[File:MANXYZ permease Step 4.jpg|thumb|450px|right|upright|Lambda phage J protein interaction with the LamB porin]]

Lambda phage is a non-contractile tailed phage, meaning during an infection event it cannot 'force' its DNA through a bacterial cell membrane. It must instead use an existing pathway to invade the host cell, having evolved the tip of its tail to interact with a specific pore to allow entry of its DNA to the hosts.
# Bacteriophage Lambda binds to an ''E. coli'' cell by means of its J protein in the tail tip. The J protein interacts with the maltose outer membrane [[porin (protein)|porin]] (the product of the ''lamB'' gene) of ''E. coli'',<ref>{{cite journal | vauthors = Werts C, Michel V, Hofnung M, Charbit A | title = Adsorption of bacteriophage lambda on the LamB protein of Escherichia coli K-12: point mutations in gene J of lambda responsible for extended host range | journal = Journal of Bacteriology | volume = 176 | issue = 4 | pages = 941–947 | date = February 1994 | pmid = 8106335 | pmc = 205142 | doi = 10.1128/jb.176.4.941-947.1994 }}</ref> a porin molecule, which is part of the [[maltose]] operon.
# The linear phage genome is injected through the outer membrane.
# The DNA passes through the mannose permease complex in the inner membrane<ref>{{cite journal | vauthors = Erni B, Zanolari B, Kocher HP | title = The mannose permease of Escherichia coli consists of three different proteins. Amino acid sequence and function in sugar transport, sugar phosphorylation, and penetration of phage lambda DNA | journal = The Journal of Biological Chemistry | volume = 262 | issue = 11 | pages = 5238–5247 | date = April 1987 | pmid = 2951378 | doi = 10.1016/S0021-9258(18)61180-9 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Liu X, Zeng J, Huang K, Wang J | title = Structure of the mannose transporter of the bacterial phosphotransferase system | journal = Cell Research | volume = 29 | issue = 8 | pages = 680–682 | date = August 2019 | pmid = 31209249 | pmc = 6796895 | doi = 10.1038/s41422-019-0194-z }}</ref>  (encoded by the manXYZ genes) and immediately circularises using the ''cos'' sites, 12-base G-C-rich cohesive "sticky ends". The single-strand viral DNA ends are ligated by host [[DNA ligase]].  It is not generally appreciated that the 12 bp lambda cohesive ends were the subject of the first direct nucleotide sequencing of a biological DNA.<ref name="src3"/>

[[File:MANXYZ permease Step 10.jpg|thumb|350px|right|Lambda phage DNA injection into the cell membrane using Mannose PTS permease (a sugar transporting system) as a mechanism of entry into the cytoplasm]]

# Host [[DNA gyrase]] puts negative [[supercoil]]s in the circular chromosome, causing A-T-rich regions to unwind and drive transcription.
# Transcription starts from the constitutive ''P<sub>L</sub>'', ''P<sub>R</sub>'' and ''P<sub>R'</sub>'' [[promoter (biology)|promoters]] producing the 'immediate early' transcripts. At first, these express the ''N'' and ''cro'' genes, producing N, Cro and a short inactive protein.

[[File:N protien.svg|thumb|200px|Early activation events involving N protein]]

# Cro binds to ''OR3'', preventing access to the ''P<sub>RM</sub>'' promoter, preventing expression of the ''cI'' gene. N binds to the two ''Nut'' (N utilisation) sites, one in the ''N'' gene in the ''P<sub>L</sub>'' reading frame, and one in the ''cro'' gene in the ''P<sub>R</sub>'' reading frame.
# The N protein is an [[antiterminator]], and functions by engaging the transcribing [[RNA polymerase]] at specific sites of the nascently transcribed mRNA. When [[RNA polymerase]] transcribes these regions, it recruits N and forms a complex with several host Nus proteins. This complex skips through most termination sequences. The extended transcripts (the 'late early' transcripts) include the ''N'' and ''cro'' genes along with ''cII'' and ''cIII'' genes, and ''xis'', ''int'', ''O'', ''P'' and ''Q'' genes discussed later.
# The cIII protein acts to protect the cII protein from proteolysis by FtsH (a membrane-bound essential ''E''. ''coli'' protease) by acting as a competitive inhibitor. This inhibition can induce a [[bacteriostatic]] state, which favours lysogeny. cIII also directly stabilises the cII protein.<ref>{{cite journal | vauthors = Kobiler O, Rokney A, Oppenheim AB | title = Phage lambda CIII: a protease inhibitor regulating the lysis-lysogeny decision | journal = PLOS ONE | volume = 2 | issue = 4 | pages = e363 | date = April 2007 | pmid = 17426811 | pmc = 1838920 | doi = 10.1371/journal.pone.0000363 | doi-access = free | bibcode = 2007PLoSO...2..363K }}</ref>
On initial infection, the stability of [[CII protein|cII]] determines the lifestyle of the phage; stable cII will lead to the lysogenic pathway, whereas if [[CII protein|cII]] is degraded the phage will go into the lytic pathway. Low temperature, starvation of the cells and high [[multiplicity of infection]] (MOI) are known to favor lysogeny (see later discussion).<ref>{{cite book |last1=Henkin |first1=Tina M. |last2=Peters |first2=Joseph E. |title=Snyder and Champness molecular genetics of bacteria |date=2020 |publisher=John Wiley & Sons, Inc |location=Hoboken, NJ |isbn=9781555819750 |pages=293–294 |edition=Fifth |chapter=Bacteriophages and Transduction}}</ref>

==== N antitermination ====
{{multiple image
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|width = 400
|footer =N Antitermination requires the assembly of a large ribonucleoprotein complex to effectively prolong the anti-termination process, without the full  complex the RNA polymerase is able to bypass only a single terminator<ref name="Korlach 2008">{{cite journal | vauthors = Santangelo TJ, Artsimovitch I | title = Termination and antitermination: RNA polymerase runs a stop sign | journal = Nature Reviews. Microbiology | volume = 9 | issue = 5 | pages = 319–329 | date = May 2011 | pmid = 21478900 | pmc = 3125153 | doi = 10.1038/nrmicro2560 }}</ref>

| image1    =Nantitermination1.jpg

| image2    = Nantitermination2.jpg
}}
This occurs without the N protein interacting with the DNA; the protein instead binds to the freshly transcribed mRNA. Nut sites contain 3 conserved "boxes", of which only BoxB is essential.
# The boxB RNA sequences are located close to the 5' end of the pL and pR transcripts. When transcribed, each sequence forms a hairpin loop structure that the N protein can bind to.
# N protein binds to boxB in each transcript, and contacts the transcribing RNA polymerase via RNA looping. The N-RNAP complex is stabilized by subsequent binding of several host Nus (N utilisation substance) proteins (which include transcription termination/antitermination factors and, bizarrely, a ribosome subunit).
# The entire complex (including the bound ''Nut'' site on the mRNA) continues transcription, and can skip through termination sequences.

===Lytic life cycle===
{{Main|Lytic cycle}}
[[File:LambdaPlaques.jpg|thumb|Lysis plaques of lambda phage on ''[[Escherichia coli|E. coli]]'' bacteria]]
This is the lifecycle that the phage follows following most infections, where the cII protein does not reach a high enough concentration due to degradation, so does not activate its promoters.{{citation needed|date=October 2022}}
# The 'late early' transcripts continue being written, including ''xis'', ''int'', ''Q'' and genes for replication of the lambda genome (''OP''). Cro dominates the repressor site (see [[#Repressor|"Repressor" section]]), repressing synthesis from the ''P<sub>RM</sub>'' promoter  (which is a promoter of the lysogenic cycle).
# The O and P proteins initiate replication of the phage chromosome (see "Lytic Replication").
# Q, another [[antiterminator]], binds to ''Qut'' sites.
# Transcription from the ''P<sub>R'</sub>'' promoter can now extend to produce mRNA for the lysis and the head and tail proteins.
# Structural proteins and phage genomes self-assemble into new phage particles.
# Products of the genes ''S'',''R'', ''Rz'' and ''Rz1'' cause cell lysis. S is a [[holin]], a small membrane protein that, at a time determined by the sequence of the protein, suddenly makes holes in the membrane. R is an [[endolysin]], an enzyme that escapes through the S holes and cleaves the cell wall. Rz and Rz1 are membrane proteins that form a complex that somehow destroys the outer membrane, after the endolysin has degraded the cell wall. For wild-type lambda, lysis occurs at about 50 minutes after the start of infection and releases around 100 virions.

====Rightward transcription====
Rightward transcription expresses the ''O'', ''P'' and ''Q'' genes. O and P are responsible for initiating replication, and Q is another antiterminator that allows the expression of head, tail, and lysis genes from ''P<sub>R’</sub>''.<ref name="src3"/>

Pr is the promoter for rightward transcription, and the cro gene is a regulator gene. The cro gene will encode for the Cro protein that will then repress Prm promoter.  Once Pr transcription is underway the Q gene will then be transcribed at the far end of the operon for rightward transcription. The Q gene is a regulator gene found on this operon, which will control the expression of later genes for rightward transcription. Once the gene's regulatory proteins allow for expression, the Q protein will then act as an anti-terminator. This will then allow for the rest of the operon to be read through until it reaches the transcription terminator. Thus allowing expression of later genes in the operon, and leading to the expression of the lytic cycle.<ref>{{cite journal | vauthors = Thomason LC, Schiltz CJ, Court C, Hosford CJ, Adams MC, Chappie JS, Court DL | title = Bacteriophage λ RexA and RexB functions assist the transition from lysogeny to lytic growth | journal = Molecular Microbiology | volume = 116 | issue = 4 | pages = 1044–1063 | date = October 2021 | pmid = 34379857 | pmc = 8541928 | doi = 10.1111/mmi.14792 }}</ref>

Pr promoter has been found to activate the origin in the use of rightward transcription, but the whole picture of this is still somewhat misunderstood. Given there are some caveats to this, for instance this process is different for other phages such as N15 phage, which may encode for DNA polymerase. Another example is the P22 phage may replace the p gene, which encodes for an essential replication protein for something that is capable of encoding for a DnaB helices.<ref name="src3"/>

====Lytic replication====
# For the first few replication cycles, the lambda genome undergoes [[Theta structure|θ replication]] (circle-to-circle).
# This is initiated at the ''ori'' site located in the ''O'' gene. O protein binds the ''ori'' site, and P protein binds the DnaB subunit of the host replication machinery as well as binding O. This effectively commandeers the host DNA polymerase.
# Soon, the phage switches to a [[rolling circle replication]] similar to that used by phage M13. The DNA is nicked and the 3’ end serves as a primer. Note that this does not release single copies of the phage genome but rather one long molecule with many copies of the genome: a [[concatemer]].
# These concatemers are cleaved at their ''cos'' sites as they are packaged. Packaging cannot occur from circular phage DNA, only from concatomeric DNA.

====Q antitermination====
{{multiple image
| width     = 400
|direction = vertical
|align = center
|footer =  The Q protein modifies the RNA polymerase at the promoter region and is  recruited to RNA polymerase. The Q protein turns into a RNA polymerase subunit after it is recruitment to RNAP and modifies the enzyme into a processive state.  Note that NusA can stimulate the activity of the Q protein.<ref name="Korlach 2008">{{cite journal | vauthors = Santangelo TJ, Artsimovitch I | title = Termination and antitermination: RNA polymerase runs a stop sign | journal = Nature Reviews. Microbiology | volume = 9 | issue = 5 | pages = 319–329 | date = May 2011 | pmid = 21478900 | pmc = 3125153 | doi = 10.1038/nrmicro2560 }}</ref>

| image1    =Qantitermination1.jpg|
| alt1      = Step 1

|image2 = QantiterminationSupplement.jpg

| image3    = Qantitermination2.jpg
| alt3      = Step 2
}}
Q is similar to N in its effect: Q binds to [[RNA polymerase]] in ''Qut'' sites and the resulting complex can ignore terminators, however the mechanism is very different; the Q protein first associates with a DNA sequence rather than an mRNA sequence.<ref name="Deighan, P. and Hochschild, A.">{{cite journal | vauthors = Deighan P, Hochschild A | title = The bacteriophage lambdaQ anti-terminator protein regulates late gene expression as a stable component of the transcription elongation complex | journal = Molecular Microbiology | volume = 63 | issue = 3 | pages = 911–920 | date = February 2007 | pmid = 17302807 | doi = 10.1111/j.1365-2958.2006.05563.x | doi-access = free }}</ref>
# The ''Qut'' site is very close to the ''P<sub>R’</sub>'' promoter, close enough that the σ factor has not been released from the RNA polymerase holoenzyme. Part of the ''Qut'' site resembles the -10 [[Pribnow box]], causing the holoenzyme to pause.
# Q protein then binds and displaces part of the σ factor and transcription re-initiates.
# The head and tail genes are transcribed and the corresponding proteins self-assemble.

====Leftward transcription====
[[File:Phage Lambda int xis Retroregulation.jpg|thumb|right|300px|Diagram showing the retro-regulation process that yields a higher concentration of xis compared to int. The mRNA transcript is digested by bacterial RNase starting from the cleaved hairpin loop at sib.]]
Leftward transcription expresses the ''gam,'' ''xis'', ''bar'' and ''int'' genes.<ref name="src3"/> Gam proteins are involved in recombination. Gam is also important in that it inhibits the host RecBCD nuclease from degrading the 3’ ends in rolling circle replication. Int and xis are integration and excision proteins vital to lysogeny.{{Citation needed|date=November 2023}}

===== Leftward transcription process =====

# Lambda phage inserts chromosome into the cytoplasm of the host bacterial cell.
# The phage chromosome is inserted to the host bacterial chromosome through DNA ligase.
# Transcription of the phage chromosome proceeds leftward when the host RNA polymerase attaches to promotor site ''p''L resulting in the translation of gene ''N.''
## Gene N acts a regulatory gene that results in RNA polymerase being unable to recognize translation-termination sites.<ref name="pmid6241940">{{cite journal | vauthors = Brammar WJ, Hadfield C | title = A programme for the construction of a lambda phage | journal = Journal of Embryology and Experimental Morphology | volume = 83 | issue = Suppl | pages = 75–88 | date = November 1984 | pmid = 6241940 | doi = | url = }}</ref>

===== Leftward Transcription mutations =====
Leftward transcription is believed to result in a deletion mutation of the ''rap'' gene resulting in a lack of growth of lambda phage. This is due to RNA polymerase attaching to pL promoter site instead of the pR promotor site. Leftward transcription results in ''bar''I and ''bar''II transcription on the left operon. Bar  positive phenotype is present when the ''rap'' gene is absent. The lack of growth of lambda phage is believed to occur due to a temperature sensitivity resulting in inhibition of growth.<ref>{{cite journal | vauthors = Guzmán P, Guarneros G | title = Phage genetic sites involved in lambda growth inhibition by the Escherichia coli rap mutant | journal = Genetics | volume = 121 | issue = 3 | pages = 401–409 | date = March 1989 | pmid = 2523838 | pmc = 1203628 | doi = 10.1093/genetics/121.3.401 }}</ref>

===== xis and int regulation of insertion and excision =====
# ''xis'' and ''int'' are found on the same piece of mRNA, so approximately equal concentrations of ''xis'' and ''int'' proteins are produced. This results (initially) in the excision of any inserted genomes from the host genome.
# The mRNA from the ''P<sub>L</sub>'' promoter forms a stable secondary structure with a [[stem-loop]] in the ''sib'' section of the mRNA. This targets the 3' (''sib'') end of the mRNA for RNAaseIII degradation, which results in a lower effective concentration of ''int'' mRNA than ''xis'' mRNA (as the ''int'' cistron is nearer to the ''sib'' sequence than the ''xis'' cistron is to the ''sib'' sequence), so a higher concentrations of ''xis'' than ''int'' is observed.
# Higher concentrations of ''xis'' than ''int'' result in no insertion or excision of phage genomes, the evolutionarily favoured action - leaving any pre-inserted phage genomes inserted (so reducing competition) and preventing the insertion of the phage genome into the genome of a doomed host.

===Lysogenic (or lysenogenic) life cycle===
{{Main|Lysogenic cycle}}
The lysogenic lifecycle begins once the cI protein reaches a high enough concentration to activate its promoters, after a small number of infections.
# The 'late early' transcripts continue being written, including ''xis'', ''int'', ''Q'' and genes for replication of the lambda genome.
# The stabilized cII acts to promote transcription from the ''P<sub>RE</sub>'', ''P<sub>I</sub>'' and ''P<sub>antiq</sub>'' promoters.
# The ''P<sub>antiq</sub>'' promoter produces antisense mRNA to the ''Q'' gene message of the ''P<sub>R</sub>'' promoter transcript, thereby switching off Q production. The ''P<sub>RE</sub>'' promoter produces antisense mRNA to the cro section of the ''P<sub>R</sub>'' promoter transcript, turning down cro production, and has a transcript of the ''cI'' gene. This is expressed, turning on cI repressor production. The ''P<sub>I</sub>'' promoter expresses the ''int'' gene, resulting in high concentrations of Int protein. This int protein integrates the phage DNA into the host chromosome (see "Prophage Integration").
# No Q results in no extension of the ''P<sub>R'</sub>'' promoter's reading frame, so no lytic or structural proteins are made. Elevated levels of int (much higher than that of xis) result in the insertion of the lambda genome into the hosts genome (see diagram). Production of cI leads to the binding of cI to the ''OR1'' and ''OR2'' sites in the ''P<sub>R</sub>'' promoter, turning off  ''cro'' and other early gene expression. cI also binds to the ''P<sub>L</sub>'' promoter, turning off transcription there too.
# Lack of cro leaves the ''OR3'' site unbound, so transcription from the ''P<sub>RM</sub>'' promoter may occur, maintaining levels of cI.
# Lack of transcription from the ''P<sub>L</sub>'' and ''P<sub>R</sub>'' promoters leads to no further production of cII and cIII.
# As cII and cIII concentrations decrease, transcription from the ''P<sub>antiq</sub>'', ''P<sub>RE</sub>'' and ''P<sub>I</sub>'' stop being promoted since they are no longer needed.
# Only the ''P<sub>RM</sub>'' and ''P<sub>R'</sub>'' promoters are left active, the former producing cI protein and the latter a short inactive transcript. The genome remains inserted into the host genome in a dormant state.

The prophage is duplicated with every subsequent cell division of the host. The phage genes expressed in this dormant state code for proteins that repress expression of other phage genes (such as the structural and lysis genes) in order to prevent entry into the lytic cycle. These repressive proteins are broken down when the host cell is under stress, resulting in the expression of the repressed phage genes. Stress can be from [[starvation]], [[poison]]s (like [[antibiotics]]), or other factors that can damage or destroy the host. In response to stress, the activated prophage is excised from the DNA of the host cell by one of the newly expressed gene products and enters its lytic pathway.

====Prophage integration====
The integration of phage λ takes place at a special attachment site in the bacterial and phage genomes, called ''att<sup>λ</sup>''. The sequence of the bacterial att site is called ''attB'', between the ''gal'' and ''bio'' operons, and consists of the parts B-O-B', whereas the complementary sequence in the circular phage genome is called ''attP'' and consists of the parts P-O-P'. The integration itself is a sequential exchange (see [[genetic recombination]]) via a [[Holliday junction]] and requires both the phage protein Int and the bacterial protein IHF (''integration host factor''). Both Int and IHF bind to ''attP'' and form an intasome, a DNA-protein-complex designed for [[site-specific recombination]] of the phage and host DNA. The original B-O-B' sequence is changed by the integration to B-O-P'-phage DNA-P-O-B'. The phage DNA is now part of the host's genome.<ref>{{cite journal | vauthors = Groth AC, Calos MP | title = Phage integrases: biology and applications | journal = Journal of Molecular Biology | volume = 335 | issue = 3 | pages = 667–678 | date = January 2004 | pmid = 14687564 | doi = 10.1016/j.jmb.2003.09.082 }}</ref>

====Maintenance of lysogeny====
[[File:Phage Lambda Integration Excision.jpg|thumb|right|upright=1.75|A simplified representation of the integration/excision paradigm and the major genes involved.]]
* Lysogeny is maintained solely by cI. cI represses transcription from ''P<sub>L</sub>'' and ''P<sub>R</sub>'' while upregulating and controlling its own expression from ''P<sub>RM</sub>''. It is therefore the only protein expressed by lysogenic phage.
[[File:Polymerase cl protien.svg|thumb|Lysogen repressors and polymerase bound to OR1 and recruits OR2, which will activate PRM and shutdown PR.]]
* This is coordinated by the ''P<sub>L</sub>'' and ''P<sub>R</sub>'' operators. Both operators have three binding sites for cI: ''OL1'', ''OL2'', and ''OL3'' for ''P<sub>L</sub>'', and ''OR1'', ''OR2'' and ''OR3'' for ''P<sub>R</sub>''.
* cI binds most favorably to ''OR1''; binding here inhibits transcription from ''P<sub>R</sub>''. As cI easily dimerises, the binding of cI to ''OR1'' greatly increases the affinity of the binding of cI to ''OR2'', and this happens almost immediately after ''OR1'' binding. This activates transcription in the other direction from ''P<sub>RM</sub>'', as the N terminal domain of cI on ''OR2'' tightens the binding of RNA polymerase to ''P<sub>RM</sub>'' and hence cI stimulates its own transcription. When it is present at a much higher concentration, it also binds to ''OR3'', inhibiting transcription from ''P<sub>RM</sub>'', thus regulating its own levels in a [[negative feedback]] loop.
* cI binding to the ''P<sub>L</sub>'' operator is very similar, except that it has no direct effect on cI transcription. As an additional repression of its own expression, however, cI dimers bound to ''OR3'' and ''OL3'' bend the DNA between them to tetramerise.
* The presence of cI causes immunity to superinfection by other lambda phages, as it will inhibit their ''P<sub>L</sub>'' and ''P<sub>R</sub>'' promoters.

====Induction====
[[File:Phage Lambda SwitchStates.jpg|thumb|200px|upright=1.5|Transcriptional state of the P<sub>RM</sub> and P<sub>R</sub> promoter regions during a lysogenic state vs induced, early lytic state.]]
The classic induction of a lysogen involved irradiating the infected cells with UV light. Any situation where a lysogen undergoes DNA damage or the [[SOS response]] of the host is otherwise stimulated leads to induction.
# The host cell, containing a dormant phage genome, experiences DNA damage due to a high stress environment, and starts to undergo the [[SOS response]].
# RecA (a cellular protein) detects DNA damage and becomes activated. It is now RecA*, a highly specific co-protease.
# Normally RecA* binds LexA (a [[transcription (genetics)|transcription]] repressor), activating LexA auto-protease activity, which destroys LexA repressor, allowing production of [[DNA repair]] proteins. In lysogenic cells, this response is hijacked, and RecA* stimulates  cI autocleavage. This is because cI mimics the structure of LexA at the autocleavage site.
# Cleaved cI can no longer dimerise, and loses its affinity for DNA binding.
# The ''P<sub>R</sub>'' and ''P<sub>L</sub>'' promoters are no longer repressed and switch on, and the cell returns to the lytic sequence of expression events (note that cII is not stable in cells undergoing the SOS response). There is however one notable difference.
[[File:Lambda phage LexA inihibition.svg|thumb|right|200px|The function of LexA in the SOS response.  LexA expression leads to inhibition of various genes including LexA.]]

====Control of phage genome excision in induction====
# The phage genome is still inserted in the host genome and needs excision for DNA replication to occur. The ''sib'' section beyond the normal ''P<sub>L</sub>'' promoter transcript is, however, no longer included in this reading frame (see diagram).
# No ''sib'' domain on the ''P<sub>L</sub>'' promoter mRNA results in no hairpin loop on the 3' end, and the transcript is no longer targeted for RNAaseIII degradation.
# The new intact transcript has one  copy of both ''xis'' and ''int'', so approximately equal concentrations of xis and int proteins are produced.
# Equal concentrations of xis and int result in the excision of the inserted genome from the host genome for replication and later phage production.

==Multiplicity reactivation and prophage reactivation==
Multiplicity reactivation (MR) is the process by which multiple viral genomes, each containing inactivating genome damage, interact within an infected cell to form a viable viral genome. MR was originally discovered with phage T4, but was subsequently found in phage λ (as well as in numerous other bacterial and mammalian viruses<ref>{{cite journal | vauthors = Michod RE, Bernstein H, Nedelcu AM | title = Adaptive value of sex in microbial pathogens | journal = Infection, Genetics and Evolution | volume = 8 | issue = 3 | pages = 267–285 | date = May 2008 | pmid = 18295550 | doi = 10.1016/j.meegid.2008.01.002 }}</ref>).  MR of phage λ inactivated by UV light depends on the recombination function of either the host or of the infecting phage.<ref>{{cite journal | vauthors = Huskey RJ | title = Multiplicity reactivation as a test for recombination function | journal = Science | volume = 164 | issue = 3877 | pages = 319–320 | date = April 1969 | pmid = 4887562 | doi = 10.1126/science.164.3877.319 | s2cid = 27435591 | bibcode = 1969Sci...164..319H }}</ref>  Absence of both recombination systems leads to a loss of MR.

Survival of UV-irradiated phage λ is increased when the E. coli host is lysogenic for an homologous prophage, a phenomenon termed prophage reactivation.<ref>{{cite journal | vauthors = Blanco M, Devoret R | title = Repair mechanisms involved in prophage reactivation and UV reactivation of UV-irradiated phage lambda | journal = Mutation Research | volume = 17 | issue = 3 | pages = 293–305 | date = March 1973 | pmid = 4688367 | doi = 10.1016/0027-5107(73)90001-8 }}</ref>  Prophage reactivation in phage λ appears to occur by a recombinational repair process similar to that of MR.

==Repressor==
[[File:Lambda phage temperate controls.png|thumbnail|right|Protein interactions that lead to either Lytic or Lysogenic cycles for Lambda phage]]
The [[repressor]] found in the phage lambda is a notable example of the level of control possible over gene expression by a very simple system. As discovered by [[Barbara J. Meyer]],<ref>{{cite web | url = http://www.hhmi.org/biointeractive/gender/meyer.html | title = Barbara J. Meyer | work = [[HHMI]] Interactive }}</ref> it forms a 'binary switch' with two genes under mutually exclusive expression. 

[[File:LambdaPhage Repressor Cooperativity.jpg|thumb|right|upright=1.75|Visual representation of repressor tetramer/octamer binding to phage lambda L and R operator sites (stable lysogenic state)]]

The lambda repressor gene system consists of (from left to right on the chromosome):
* ''cI'' gene
* O<sub>R</sub>3
* O<sub>R</sub>2
* O<sub>R</sub>1
* ''cro'' gene

The lambda repressor is a self assembling dimer also known as the cI protein.<ref name="pmid8031775">{{cite journal | vauthors = Burz DS, Beckett D, Benson N, Ackers GK | title = Self-assembly of bacteriophage lambda cI repressor: effects of single-site mutations on the monomer-dimer equilibrium | journal = Biochemistry | volume = 33 | issue = 28 | pages = 8399–8405 | date = July 1994 | pmid = 8031775 | doi = 10.1021/bi00194a003 }}</ref> It binds DNA in the helix-turn-helix binding motif. It regulates the transcription of the cI protein and the Cro protein.

The life cycle of lambda phages is controlled by cI and Cro proteins. The lambda phage will remain in the lysogenic state if cI proteins predominate, but will be transformed into the lytic cycle if cro proteins predominate.

The cI dimer may bind to any of three operators, O<sub>R</sub>1, O<sub>R</sub>2, and O<sub>R</sub>3, in the order O<sub>R</sub>1 > O<sub>R</sub>2 > O<sub>R</sub>3.
Binding of a cI dimer to O<sub>R</sub>1 enhances binding of a second cI dimer to O<sub>R</sub>2, an effect called [[cooperativity]]. Thus,  O<sub>R</sub>1 and O<sub>R</sub>2 are almost always simultaneously occupied by cI. However, this does not increase the affinity between cI and O<sub>R</sub>3, which will be occupied only when the cI concentration is high.

At high concentrations of cI, the dimers will also bind to operators O<sub>L</sub>1 and O<sub>L</sub>2 (which are over 2 kb downstream from the R operators). When cI dimers are bound to O<sub>L</sub>1, O<sub>L</sub>2, O<sub>R</sub>1, and O<sub>R</sub>2 a loop is induced in the DNA, allowing these dimers to bind together to form an octamer. This is a phenomenon called ''long-range cooperativity''. Upon formation of the octamer, cI dimers may cooperatively bind to O<sub>L</sub>3 and O<sub>R</sub>3, repressing transcription of cI. This ''autonegative'' regulation ensures a stable minimum concentration of the repressor molecule and, should SOS signals arise, allows for more efficient prophage induction.<ref>{{cite book | vauthors = Ptashne M |title=A genetic switch: phage lambda revisited |date=2004 |publisher=Cold Spring Harbor Laboratory Press |location=Cold Spring Harbor, NY |isbn=978-0-87969-716-7 |edition=3rd | page = 112 }}</ref>
* In the absence of cI proteins, the ''cro'' gene may be transcribed.
* In the presence of cI proteins, only the ''cI'' gene may be transcribed.
* At high concentration of cI, transcriptions of both genes are repressed.

<gallery>
File:Viral DNA setup.svg|Some base pairs with serve a dual function with promoter and operator for either cl and cro proteins.
File:Polymerase ON.svg|Protein cl turned ON, with repressor bound to OR2 polymerase binding is increased and turn OFF OR1.
File:Repressor concentration.svg|Lysogen repression all 3 sites bound is a low occurrence due to OR3 weak binding affinity.  OR1 repression increases binding affinity to OR2 due to repressor-repressor interaction.  Increased concentrations of repressor increase binding.
</gallery>

==Protein function overview==
{| class="wikitable"
! scope="col" width="150px" | Protein
! scope="col" width="150px" | Function in life cycle
! scope="col" width="90px" | Promoter region
! scope="col" width="600px" | Description
|-
| cIII || Regulatory protein CIII.  Lysogeny, cII Stability || P<sub>L</sub> || (Clear 3) ''HflB'' (FtsH) binding protein, protects ''cII'' from degradation by proteases.
|-
| cII || Lysogeny, Transcription activator || P<sub>R</sub> || (Clear 2) Activates transcription from the P<sub>AQ</sub>, P<sub>RE</sub> and P<sub>I</sub> promoters, transcribing ''cI'' and ''int''. Low stability due to susceptibility to cellular ''HflB'' (FtsH) proteases (especially in healthy cells and cells undergoing the SOS response). High levels of ''cII'' will push the phage toward integration and lysogeny while low levels of ''cII'' will result in lysis.
|-
| cI || Repressor, Maintenance of Lysogeny || P<sub>RM</sub>, P<sub>RE</sub> || (Clear 1) Transcription inhibitor, binds O<sub>R</sub>1, O<sub>R</sub>2 and O<sub>R</sub>3 (affinity O<sub>R</sub>1 > O<sub>R</sub>2 = O<sub>R</sub>3, i.e. preferentially binds O<sub>R</sub>1). At low concentrations blocks the P<sub>R</sub> promoter (preventing cro production). At high concentrations downregulates its own production through O<sub>R</sub>3 binding. Repressor also inhibits transcription from the P<sub>L</sub> promoter. Susceptible to cleavage by ''[[RecA]]*'' in cells undergoing the SOS response.
|-
| cro || Lysis, Control of Repressor's Operator || P<sub>R</sub> || Transcription inhibitor, binds O<sub>R</sub>3, O<sub>R</sub>2 and O<sub>R</sub>1 (affinity O<sub>R</sub>3 > O<sub>R</sub>2 = O<sub>R</sub>1, i.e. preferentially binds O<sub>R</sub>3). At low concentrations blocks the pRM promoter (preventing ''cI'' production). At high concentrations downregulates its own production through O<sub>R</sub>2 and O<sub>R</sub>1 binding. No cooperative binding (cf. below for cI binding)
|-
| O || Lysis, DNA replication || P<sub>R</sub> || Replication protein O.  Initiates Phage Lambda DNA replication by binding at ''ori'' site.
|-
| P || Lysis, DNA Replication || P<sub>R</sub> || Initiates Phage Lambda DNA replication by binding to ''O'' and ''DnaB'' subunit. These bindings provide control over the host DNA polymerase.
|-
| {{anchor|gam}}gam || Lysis, DNA replication || P<sub>L</sub> || Inhibits host ''[[RecBCD]]'' nuclease from degrading 3' ends—allow [[rolling circle replication]] to proceed.
|-
| S || Lysis || P<sub>R'</sub> || [[Holin]], a membrane protein that perforates the membrane during lysis.
|-
| R || Lysis || P<sub>R'</sub> || [[Endolysin]], Lysozyme, an enzyme that exits the cell through the holes produced by Holin and cleaves apart the cell wall.
|-
| Rz and Rz1 || Lysis || P<sub>R'</sub> || Forms a membrane protein complex that destroys the outer cell membrane following the cell wall degradation by endolysin. Spanin, Rz1(outer membrane subunit) and Rz(inner membrane subunit).
|-

| F || Lysis || P<sub>R'</sub> || Phage capsid head proteins.
|-

| D || Lysis || P<sub>R'</sub> || Head decoration protein.
|-

| E || Lysis || P<sub>R'</sub> || Major head protein.
|-

| C || Lysis || P<sub>R'</sub> || Minor capsid protein.
|-

| B || Lysis || P<sub>R'</sub> || Portal protein B.
|-

| A || Lysis || P<sub>R'</sub> || Large terminase protein.
|-

| J || Lysis || P<sub>R'</sub> || Host specificity protein J.
|-

| M V U G L T Z || Lysis || P<sub>R'</sub> || Minor tail protein M.
|-

| K || Lysis || P<sub>R'</sub> || Probable endopeptidase.
|-

| H || Lysis || P<sub>R'</sub> || Tail tape measure protein H.
|-

| I || Lysis || P<sub>R'</sub> || Tail assembly protein I.
|-

| FI || Lysis || P<sub>R'</sub> || DNA-packing protein FI.
|-

| FII || Lysis || P<sub>R'</sub> || Tail attachment protein.
|-

| tfa || Lysis || P<sub>R'</sub> || Tail fiber assembly protein.
|-

| int || Genome Integration, Excision || P<sub>I</sub>, P<sub>L</sub> || [[Integrase]], manages insertion of phage genome into the host's genome. In Conditions of low ''int'' concentration there is no effect. If ''xis'' is low in concentration and ''int'' high then this leads to the insertion of the phage genome. If ''xis'' and ''int'' have high (and approximately equal) concentrations this leads to the excision of phage genomes from the host's genome.
|-
| xis || Genome Excision || P<sub>I</sub>, P<sub>L</sub> || [[Excisionase]] and ''int'' protein regulator, manages excision and insertion of phage genome into the host's genome.
|-
| N || Antitermination for Transcription of Late Early Genes || P<sub>L</sub> || [[Antiterminator]], RNA-binding protein and RNA polymerase cofactor, binds RNA (at Nut sites) and transfers onto the nascent RNApol that just transcribed the nut site. This RNApol modification prevents its recognition of termination sites, so normal RNA polymerase termination signals are ignored and RNA synthesis continues into distal phage genes (''cII, cIII, xis, int, O, P, Q'')
|-
| Q || Antitermination for Transcription of Late Lytic Genes || P<sub>R</sub> || [[Antiterminator]], DNA binding protein and RNApol cofactor, binds DNA (at Qut sites) and transfers onto the initiating RNApol. This RNApol modification alters its recognition of termination sequences, so normal ones are ignored; special Q termination sequences some 20,000 bp away are effective. Q-extended transcripts include phage structural proteins (A-F, Z-J) and lysis genes (''S, R, Rz and Rz1''). Downregulated by P''<sub>antiq</sub>'' antisense mRNA during lysogeny.
|-
| [[RecA]] || [[SOS Response]] || Host protein || DNA repair protein, functions as a co-protease during SOS response, auto-cleaving ''LexA'' and ''cI'' and facilitating lysis.
|}

==Lytic vs. lysogenic==
[[File:Lambda temperate life cycle.png|thumbnail|Diagram of temperate phage life cycle, showing both lytic and lysogenic cycles.]]
An important distinction here is that between the two decisions; lysogeny and lysis on infection, and continuing lysogeny or lysis from a prophage. The latter is determined solely by the activation of RecA in the SOS response of the cell, as detailed in the section on induction. The former will also be affected by this; a cell undergoing an SOS response will always be lysed, as no cI protein will be allowed to build up. However, the initial lytic/lysogenic decision on infection is also dependent on the cII and cIII proteins.

In cells with sufficient nutrients, protease activity is high, which breaks down cII. This leads to the lytic lifestyle. In cells with limited nutrients, protease activity is low, making cII stable. This leads to the lysogenic lifestyle. cIII appears to stabilize cII, both directly and by acting as a competitive inhibitor to the relevant proteases. This means that a cell "in trouble", i.e. lacking in nutrients and in a more dormant state, is more likely to lysogenise. This would be selected for because the phage can now lie dormant in the bacterium until it falls on better times, and so the phage can create more copies of itself with the additional resources available and with the more likely proximity of further infectable cells.

A full biophysical model for lambda's lysis-lysogeny decision remains to be developed. Computer modeling and simulation suggest that random processes during infection drive the selection of lysis or lysogeny within individual cells.<ref>{{cite journal | vauthors = Arkin A, Ross J, McAdams HH | title = Stochastic kinetic analysis of developmental pathway bifurcation in phage lambda-infected Escherichia coli cells | journal = Genetics | volume = 149 | issue = 4 | pages = 1633–1648 | date = August 1998 | pmid = 9691025 | pmc = 1460268 | doi = 10.1093/genetics/149.4.1633 }}</ref>  However, recent experiments suggest that physical differences among cells, that exist prior to infection, predetermine whether a cell will lyse or become a lysogen.<ref>{{cite journal | vauthors = St-Pierre F, Endy D | title = Determination of cell fate selection during phage lambda infection | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 105 | issue = 52 | pages = 20705–20710 | date = December 2008 | pmid = 19098103 | pmc = 2605630 | doi = 10.1073/pnas.0808831105 | doi-access = free | bibcode = 2008PNAS..10520705S }}</ref>

==As a genetic tool==
Lambda phage has been used heavily as a [[model organism]] and has been an excellent tool first in [[microbial genetics]], and then later in [[molecular genetics]].<ref>{{Citation |last1=Pitre |first1=Emmanuelle |title=Chapter Four - Understanding viral replication and transcription using single-molecule techniques |date=2021-01-01 |url=https://www.sciencedirect.com/science/article/pii/S1874604721000159 |journal=The Enzymes |volume=49 |pages=83–113 |editor-last=Cameron |editor-first=Craig E. |access-date=2023-11-28 |series=Viral Replication Enzymes and their Inhibitors Part A |publisher=Academic Press |last2=te Velthuis |first2=Aartjan J. W. |doi=10.1016/bs.enz.2021.07.005 |pmid=34696840 |s2cid=239573473 |editor2-last=Arnold |editor2-first=Jamie J. |editor3-last=Kaguni |editor3-first=Laurie S.|url-access=subscription }}</ref> Some of its uses include its application as a vector for the cloning of [[recombinant DNA]]; the use of its site-specific recombinase (int) for the shuffling of cloned DNAs by the [[Gateway Technology|gateway method]];<ref>{{Cite journal |last1=Reece-Hoyes |first1=John S. |last2=Walhout |first2=Albertha J. M. |date=2018-01-01 |title=Gateway Recombinational Cloning |url=http://cshprotocols.cshlp.org/content/2018/1/pdb.top094912 |journal=Cold Spring Harbor Protocols |language=en |volume=2018 |issue=1 |pages=pdb.top094912 |doi=10.1101/pdb.top094912 |issn=1940-3402 |pmid=29295908|pmc=5935001 }}</ref> and the application of its Red [[operon]], including the proteins Red alpha (also called 'exo'), beta and gamma in the DNA engineering method called [[recombineering]]. The 48 kb DNA fragment of lambda phage is not essential for productive infection and can be replaced by foreign DNA,<ref>{{Citation |last1=Feiss |first1=Michael |title=Bacteriophage Lambda Terminase and the Mechanism of Viral DNA Packaging |date=2013 |url=https://www.ncbi.nlm.nih.gov/books/NBK6485/ |work=Madame Curie Bioscience Database [Internet] |access-date=2023-11-28 |publisher=Landes Bioscience |language=en |last2=Catalano |first2=Carlos Enrique}}</ref> which can then be replicated by the phage. Lambda phage will enter bacteria more easily than plasmids, making it a useful vector that can either destroy or become part of the host's DNA.<ref>{{Cite journal |last=Smith |first=George P. |date=1985 |title=Filamentous Fusion Phage: Novel Expression Vectors that Display Cloned Antigens on the Virion Surface |url=https://www.jstor.org/stable/1694587 |journal=Science |volume=228 |issue=4705 |pages=1315–1317 |doi=10.1126/science.4001944 |jstor=1694587 |pmid=4001944 |bibcode=1985Sci...228.1315S |issn=0036-8075|url-access=subscription }}</ref> Lambda phage can also be manipulated and used as an anti-cancer vaccine that targets human [[ASPH|aspartyl (asparaginyl) β-hydroxylase]] (ASPH, HAAH), which has been shown to be beneficial in cases of hepatocellular carcinoma in mice.<ref>{{Cite journal |last1=Iwagami |first1=Yoshifumi |last2=Casulli |first2=Sarah |last3=Nagaoka |first3=Katsuya |last4=Kim |first4=Miran |last5=Carlson |first5=Rolf I. |last6=Ogawa |first6=Kosuke |last7=Lebowitz |first7=Michael S. |last8=Fuller |first8=Steve |last9=Biswas |first9=Biswajit |last10=Stewart |first10=Solomon |last11=Dong |first11=Xiaoqun |last12=Ghanbari |first12=Hossein |last13=Wands |first13=Jack R. |year=2017 |title=Lambda phage-based vaccine induces antitumor immunity in hepatocellular carcinoma |journal=[[Heliyon]] |language=en |volume=3 |issue=9 |pages=e00407 |doi=10.1016/j.heliyon.2017.e00407 |doi-access=free |pmc=5619992 |pmid=28971150|bibcode=2017Heliy...300407I }}</ref> Lambda phage has also been of major importance in the study of [[Transduction (genetics)|specialized transduction]].<ref>{{Cite web |date=2017-05-17 |title=7.14E: Bacteriophage Lambda as a Cloning Vector |url=https://bio.libretexts.org/Bookshelves/Microbiology/Microbiology_(Boundless)/07%3A_Microbial_Genetics/7.14%3A_Cloning_Techniques/7.14E%3A_Bacteriophage_Lambda_as_a_Cloning_Vector |access-date=2023-11-28 |website=Biology LibreTexts |language=en}}</ref>

== See also ==
* [[Esther Lederberg]]
* [[Lambda holin family]]
* [[Molecular weight size marker]]
* [[Sankar Adhya]]
* [[Zygotic induction]]
* [[Corynebacteriophage]]s – Corynephages β (beta) and ω (omega) are (proposed) members of genus ''Lambdavirus''

== References ==
{{Reflist|32em}}

== Further reading ==
{{refbegin|32em}}
* {{cite book | vauthors = Watson J, Baker T, Bell S, Gann A, Levine M, Losick R | title = Molecular Biology of the Gene (International Edition) | edition = 6th  }}
* {{cite journal | vauthors = Ptashne M, Hopkins N | author-link1 = Mark Ptashne | author-link2 = Nancy Hopkins (scientist) | title = The operators controlled by the lambda phage repressor | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 60 | issue = 4 | pages = 1282–7 | date = August 1968 | pmid = 5244737 | pmc = 224915 | doi = 10.1073/pnas.60.4.1282 | bibcode = 1968PNAS...60.1282P | doi-access = free }}
* {{cite journal | vauthors = Meyer BJ, Kleid DG, Ptashne M | title = Lambda repressor turns off transcription of its own gene | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 72 | issue = 12 | pages = 4785–89 | date = December 1975 | pmid = 1061069 | pmc = 388816 | doi = 10.1073/pnas.72.12.4785 | bibcode = 1975PNAS...72.4785M | doi-access = free }}
* {{cite journal | vauthors = Brüssow H, Hendrix RW | title = Phage genomics: small is beautiful | journal = Cell | volume = 108 | issue = 1 | pages = 13–16 | date = January 2002 | pmid = 11792317 | doi = 10.1016/S0092-8674(01)00637-7 | doi-access = free }}
* {{cite journal | vauthors = Dodd IB, Shearwin KE, Egan JB | title = Revisited gene regulation in bacteriophage lambda | journal = Current Opinion in Genetics & Development | volume = 15 | issue = 2 | pages = 145–152 | date = April 2005 | pmid = 15797197 | doi = 10.1016/j.gde.2005.02.001 }}
* {{cite journal | vauthors = Friedman DI, Court DL | title = Bacteriophage lambda: alive and well and still doing its thing | journal = Current Opinion in Microbiology | volume = 4 | issue = 2 | pages = 201–207 | date = April 2001 | pmid = 11282477 | doi = 10.1016/S1369-5274(00)00189-2 }}
* {{cite journal | vauthors = Gottesman ME, Weisberg RA | title = Little lambda, who made thee? | journal = Microbiology and Molecular Biology Reviews | volume = 68 | issue = 4 | pages = 796–813 | date = December 2004 | pmid = 15590784 | pmc = 539004 | doi = 10.1128/MMBR.68.4.796-813.2004 }}
* {{cite journal | vauthors = Hendrix RW, Smith MC, Burns RN, Ford ME, Hatfull GF | title = Evolutionary relationships among diverse bacteriophages and prophages: all the world's a phage | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 96 | issue = 5 | pages = 2192–2197 | date = March 1999 | pmid = 10051617 | pmc = 26759 | doi = 10.1073/pnas.96.5.2192 | doi-access = free | bibcode = 1999PNAS...96.2192H }}
* {{cite journal | vauthors = Kitano H | title = Systems biology: a brief overview | journal = Science | volume = 295 | issue = 5560 | pages = 1662–1664 | date = March 2002 | pmid = 11872829 | doi = 10.1126/science.1069492 | s2cid = 2703843 | bibcode = 2002Sci...295.1662K }}
* Ptashne, M. "A Genetic Switch: Phage Lambda Revisited", 3rd edition 2003
* {{cite journal | vauthors = Ptashne M | title = Regulation of transcription: from lambda to eukaryotes | journal = Trends in Biochemical Sciences | volume = 30 | issue = 6 | pages = 275–279 | date = June 2005 | pmid = 15950866 | doi = 10.1016/j.tibs.2005.04.003 | doi-access = free }}
* {{cite book | vauthors = Snyder L, Champness W | title = Molecular Genetics of Bacteria | edition = 3rd | date = 2007 }} (Contains an informative and well illustrated overview of bacteriophage lambda)
* {{cite web | work = Splasho | url = http://splasho.com/blog/essays/bacteriophage-lambda/ | archive-url = https://web.archive.org/web/20140319191609/http://splasho.com/blog/essays/bacteriophage-lambda/ | archive-date = 19 March 2014 | title = Bacteriophage Lambda Infection }} (illustrates genes active at all stages in lifecycle)
{{refend}}

== External links ==
{{Commons category}}
{{Wikispecies|Λ-like viruses}}
* Life Cycle, [http://www.blackwellpublishing.com/wagner/animations/lambdaw/lambdaw.html Basic Animation of Lambda Lifecyecle] (illustrates infection and lytic/lysogenic pathways with some protein and transcription detail)
* [https://www.youtube.com/watch?v=sLkZ9FPHJGM Time-lapse microscopy video] from MIT showing both lysis and lysogeny by phage lambda
* [https://www.youtube.com/watch?v=_vR-J05mHhQ Lambda Phage Life cycle] (basic visual demonstration of Lambda bacteriophage life cycle)
* [https://www.ncbi.nlm.nih.gov/nuccore/9626243?report=genbank Lambda Phage genome in GenBank]
* [https://www.uniprot.org/uniprot/?query=organism:10710+keyword:1185 Lambda Phage Reference Proteome from UniProt]
* [https://www.ncbi.nlm.nih.gov/structure/?term=txid10710 Lambda Phage Protein Structures in NCBI ] (3D display of protein structures for bacteriophage Lambda)

{{Model Organisms}}
{{Nucleic acids}}
{{Taxonbar|from=Q615868}}

{{DEFAULTSORT:Lambda Phage}}
[[Category:Genetics techniques]]
[[Category:Model organisms]]
[[Category:Siphoviridae]]
[[Category:Escherichia coli]]