T4 endonuclease VII cleaves DNA containing a cisplatin adduct.
T4 endonuclease VII is an enzyme that cleaves four-way junctions and other branched DNA structures. We now show that a DNA duplex containing a single cis-diammineplatinum (II) adduct at either GpG or ApG sequences is a good substrate for precise cleavage by this enzyme. The GpG platinated DNA was cleaved more efficiently than the equivalent ApG platinated DNA. A duplex containing a trans-diammineplatinum (II) adduct at a GpTpG sequence was refractory to cleavage. We suggest that local kinking of the helix due to the chemical modification by cis-dichlorodiammineplatinum (II) could be responsible for the sensitivity of the DNA to attack by endonuclease VII, in common with the structures of many other substrates for this enzyme. These results are in keeping with a general role for T4 endonuclease VII in the repair of DNA structure, and a mechanism of substrate recognition that is based on sensitivity to axial inclination.
Department of Biochemistry, The University, Dundee, U.K.
A I
AI
Murchie
D M
DM
Lilley
D001483:Base Sequence; D002945:Cisplatin / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D018736:DNA Adducts; D004706:Endodeoxyribonucleases / Q000378:metabolism*; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity
D018736:DNA Adducts; D009838:Oligodeoxyribonucleotides; C057270:cisplatin-DNA adduct; D004247:DNA; D004706:Endodeoxyribonucleases; C035571:endodeoxyribonuclease VII; D002945:Cisplatin