Pattern of recognition of DNA by mammalian DNA topoisomerase II.
The antitumor drug VP-16 stabilizes the topoisomerase II-DNA covalent complexes formed in an intermediate step of the isomerization reaction. The location of the sites of formation of these complexes and their relative strength were studied in vitro using pBR322. Sequences alignment of the regions containing the 24 detectable sites allows to identify GCGCGC-(N) alpha-TGAC with 9 less than or equal to alpha less than or equal to 25 as the DNA sequence recognized by topoisomerase II to form a cleavable complex. Changes in the last two nucleotides of the sequence determine weaker complexes.
Fosse
P
P
Laboratoire de Biochimie et Enzymologie (INSERM U 140, CNRS UA 147), Institut Gustave Roussy, Villejuif, France.
Paoletti
C
C
Saucier
J M
JM
D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000378:metabolism*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004331:Drosophila melanogaster; D004587:Electrophoresis, Agar Gel; D004591:Electrophoresis, Polyacrylamide Gel; D007536:Isomerism; D008969:Molecular Sequence Data; D011034:Podophyllotoxin / Q000494:pharmacology
D004247:DNA; D004250:DNA Topoisomerases, Type II; D011034:Podophyllotoxin