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 by a duocarmycin.
The C-terminal domain of p53 may bind single-stranded (ss) DNA ends and catalyze renaturation of ss complementary DNA molecules, suggesting a possible direct role for p53 in DNA repair (Proc. Natl. Acad. Sci. USA, 92, 9455-9459, 1995). We found that DU-86, a duocarmycin derivative which alkylates DNA, 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 intact ssDNAs and toward eliminating DU-86-damaged ssDNA from duplex formation. These results suggest that p53, via the C-terminal domain, may play a direct role in DNA repair by preferential recognization and elimination of damaged DNA.
Yokote
H
H
Pharmacology Division, National Cancer Center Research Institute, Tokyo, Japan.
Nishio
K
K
Arioka
H
H
Kurokawa
H
H
Fukuoka
K
K
Fukumoto
H
H
Ishida
T
T
Terada
T
T
Itakura
T
T
Saijo
N
N
D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D018736:DNA Adducts / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004277:DNA, Single-Stranded / Q000378:metabolism*; D000080890:Duocarmycins; D009695:Nucleic Acid Renaturation; D011485:Protein Binding; D011760:Pyrrolidinones / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011995:Recombination, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D018906:Antineoplastic Agents, Alkylating; D018736:DNA Adducts; D004277:DNA, Single-Stranded; C092034:DU 86; D000080890:Duocarmycins; D011760:Pyrrolidinones; D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53