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.