Bacteriophage λ-based cloning vectors

lambda – E. coli bacteriophage

48.5 kb genome – 12 bp single-stranded cohesive ends

– linear form (in phage particle)

– circular form (in cell)

– ligation of cohesive ends

temperate phage – two lifestyles

lysogeny – phage dormant

– inserted in host genome

lytic growth – progeny phage produced

– host cells lysed

infection – phage particle binds to LamB gene product

– (maltose transport protein)

– phage genome injected in cell

– lysis/lysogeny decision made – cII gene

– cII protein may be degraded by host Hfl protease

– if cII degraded, get lytic growth

– if cII not degraded, phage inserts in genome

(homologous recombination

– cI repressor keeps phage dormant

– cI inactivated (SOS system)

– phage reverts to lytic growth

– lytic growth

– phage genome replicated by rolling circle replication

– produces concatemers

– linear molecules with multiple phage genomes

– requires phage Gam protein

– stops host nuclease from digesting concatemers

– phage coat protein genes expressed

– head and tail self-assemble

– phage DNA packaged in phage heads

– requires 2 cos sites (cohesive packaging sites)

– must be 78%-105% of phage genome apart

– 38-52 kb apart

cos sites cleaved to 12 bp single stranded ends

– ends of phage genome

DNA sequence between cos sites – does not matter

– any DNA molecule with cos sites at right distance

– packaged in phage heads

– complete phage heads assemble – S protein lyses cell

– progeny phage released

 

lambda as cloning vector

– why use lambda?

– allows large fragments DNA to be cloned

– up to 24.6 kb – good for genomic libraries

– self-assembly of phage particles

– allows recombinant lambda to be packaged in vitro

– amplified by infecting E. coli

– large DNA fragments cloned efficiently

– screening for recombinants

– phage plaques easily screened for desired clone

– using nucleic acid probes – plaque lifts

– some vectors

– allow expression of cloned cDNAs

– can screen plaques for cloned protein

– using antibodies to protein