the presence of phage t4 dna ligase biolabs according to the recommendations of the supplier the filling of the protruding 5 u2032 ends can be performed with the klenow fragment of dna polymerase i of e coli biolabs according to the specifications of the supplier the destruction of the protruding 3 u2032 ends is performed in the presence of phage t4 dna polymerase biolabs which is used according to the recommendations of the manufacturer the destruction of the protruding 5 u2032 ends is performed by a controlled treatment with s1 nuclease the site directed mutagenesis in vitro with synthetic oligodeoxynucleotides can be carried out according to the method developed by taylor et al nucleic acids res 13 1985 8749 8764 using the kit distributed by amersham the enzymatic amplification of dna fragments by the so called pcr technique polymerase catalyzed chain reaction saiki r k et al science 230 1985 1350 1354 mullis k b and faloona f a meth enzym 155 1987 335 350 can be carried out using a u201c dna thermal cycler u201d perkin elmer cetus according to the specifications of the manufacturer the verification of the nucleotide sequences can be carried out by the method developed by sanger et al proc natl acad sci usa 74 1977 5463 5467 using the kit distributed by amersham in the following examples the following cell lines were or can be used human embryonic kidney line 293 graham et al j gen virol 36 1977 59 this line contains especially integrated in its genome the left hand part of the genome of the human adenovirus ad5 12 human cell line kb derived from a human epidermal carcinoma this line is available at atcc.