p53 stimulates human topoisomerase I activity by modulating its DNA binding.
The tumor suppressor protein p53 and the human DNA topoisomerase I (htopoI) interact with each other, which leads to a stimulation of the catalytic activity of htopoI. Moreover, p53 stimulates the topoisomerase I-induced recombination repair (TIRR) reaction. However, little was known about how p53 stimulates this topoisomerase I activity. Here we demonstrate that monomeric p53 is sufficient for the stimulation of the topoisomerase I-catalyzed relaxation activity, but the tetrameric form of p53 is required for the stimulation of TIRR. We also show that p53 stimulates topoisomerase I activity by increasing the dissociation of htopoI from DNA. Since htopoI forms a closed ring structure around the DNA, our results suggest that p53 induces a conformational change within htopoI that results in an opening of the clamp, and thereby releases htopoI from DNA.
Søe
Kent
K
Institute of Molecular Biotechnology, Department of Biochemistry, Beutenbergstrasse 11, D-07745 Jena, Germany. kent@imb-jena.de
Grosse
Frank
F
D000818:Animals; D004247:DNA / Q000378:metabolism*; D004260:DNA Repair; D004264:DNA Topoisomerases, Type I / Q000737:chemistry / Q000378:metabolism*; D019281:Dimerization; D006801:Humans; D051379:Mice; D011485:Protein Binding / Q000187:drug effects; D011487:Protein Conformation; D011995:Recombination, Genetic; D012965:Sodium Chloride / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53; D012965:Sodium Chloride; D004247:DNA; D004264:DNA Topoisomerases, Type I