The C-terminal domain of p53 catalyzes DNA-renaturation and strand exchange toward annealing between intact ssDNAs and toward eliminating damaged ssDNA from duplex formation through preferential recognition of damaged DNA bya duocarmycin

The C-terminal domain of p53 may bind single-stranded (ss) DNA ends and cat alyze renaturation of ss complementary DNA molecules, suggesting a possible direct role for p53 in DNA repair (Proc. Natl. Acad. Sci. USA, 92, 9455-94 59, 1995). We found that DU-86, a duocarmycin derivative which alkylates DN A, bound ssDNA and enhanced the DNA binding activity of the p53 C-terminus. DU-86 weakened p53-mediated catalysis of complementary ssDNA renaturation. p53 C-terminus catalyzed DNA strand transfer toward annealing between inta ct ssDNAs and toward eliminating DU-86-damaged ssDNA from duplex formation. These results suggest that p53, via the C-terminal domain, may play a dire ct role in DNA repair by preferential recognization and elimination of dama ged DNA. (C) 1998 Elsevier Science B.V. All rights reserved.