P4 phage cosmids. (a) A cosmid containing the cos sequence of phage P4 is cleaved and threaded into a viral capsid in the course of a bacterial phage infection. Circularization of the cosmid by its cohesive ends inside the phage capsid produce a highly knotted DNA circle. DNA knots are removed by topoisomerase II. (b) Scheme of circularized P4 DNA and of cosmids P4cos-8, P4cos-5 and P4cos-3, in which an EcoRI-BamH1 1189 bp fragment containing the P4-cos sequence is inserted.