Inhibition of poly(ADP-ribose)polymerase binding to DNA by thymidine dimer

The ability of poly(ADP-ribose)polymerase to bind damaged DNA was assessed by electrophoretic mobility shift assay. DNA binding domain of poly(ADP-rib ose)polymerase (PARPDBD) binds to synthetic deoxyribonucleotide duplex 10-m er, However, the synthetic deoxyribonucleotide duplex containing cys-syn th ymidine dimer which produces the unwinding of DNA helix structure lost its affinity to PARPDBD. It was shown that the binding of PARPDBD to the synthe tic deoxyribonucleotide duplex was not affected by O-6-Me-dG which causes o nly, minor distortion of DNA helix structure. This study suggests that the stabilized DNA helix structure is important for poly(ADP-ribose)polymerase binding to DNA breaks, which are known to stimulate catalytic activity of p oly(ADP-ribose)polymerase. (C) 1999 Federation of European Biochemical Soci eties.