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p53 stimulates human topoisomerase I activity by modulating its DNA binding
1Institute of Molecular Biotechnology, Department of Biochemistry, Beutenbergstrasse 11, D-07745 Jena, Germany. kent@imb-jena.de
Nucleic Acids Research
|November 7, 2003
Summary
The tumor suppressor protein p53 stimulates human DNA topoisomerase I (htopoI) activity. P53
Area of Science:
- Molecular Biology
- Biochemistry
- Genetics
Background:
- The tumor suppressor protein p53 interacts with human DNA topoisomerase I (htopoI).
- This interaction stimulates htopoI's catalytic activity and the topoisomerase I-induced recombination repair (TIRR) reaction.
- The precise mechanism by which p53 enhances htopoI activity remained unclear.
Purpose of the Study:
- To elucidate the mechanism by which p53 stimulates htopoI activity.
- To determine the role of p53 oligomerization in htopoI stimulation.
Main Methods:
- In vitro assays measuring htopoI relaxation activity.
- In vitro assays measuring TIRR.
- Analysis of p53 oligomerization states (monomeric vs. tetrameric).
Main Results:
- Monomeric p53 is sufficient to stimulate the htopoI-catalyzed relaxation of supercoiled DNA.
- The tetrameric form of p53 is required for stimulating the TIRR reaction.
- p53 enhances htopoI activity by increasing the rate of htopoI dissociation from DNA.
Conclusions:
- p53's stimulation of htopoI activity is dependent on its oligomeric state.
- p53 likely induces a conformational change in htopoI, opening its clamp-like structure.
- This conformational change facilitates htopoI release from DNA, impacting both catalytic activity and DNA repair processes.