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Papers In Press, published online ahead of print May 15, 2001
Molecular Pharmacology Department, St. Jude Children's Research Hospital, Memphis, TN 38105
Corresponding Author: john.nitiss{at}stjude.org
DNA topoisomerases play essential roles in many DNA metabolic processes. It has been suggested that topoisomerases play an essential role in DNA repair. Topoisomerases can introduce DNA damage upon exposure to drugs that stabilize the covalent protein:DNA intermediate of the topoisomerase reaction. Lesions in DNA are also able to trap topoisomerase:DNA intermediates, suggesting that topoisomerases have the potential to either assist in DNA repair by locating sites of damage, or exacerbating DNA damage by generation of additional damage at the site of a lesion. We have shown that overexpression of yeast topoisomerase I (TOP1) conferred hypersensitivity to methyl methanesulfonate, and other DNA damaging agents while expression of a catalytically inactive enzyme did not. Overexpression of topoisomerase II did not change the sensitivity of cells to these DNA damaging agents. Yeast cells y lacking TOP1 were not more resistant to DNA damage than cells expressing wild type levels of the enzyme. Yeast topoisomerase I covalent complexes can be trapped efficiently on UV damaged DNA. We suggest that TOP1 does not participate in the repair of DNA damage in yeast cells. However, the enzyme has the potential of exacerbating DNA damage by forming covalent DNA:protein complexes at sites of DNA damage.
J. Biol. Chem, 10.1074/jbc.M102674200
Submitted on March 26, 2001
Revised on May 10, 2001
Accepted on May 14, 2001
Overexpression of type I topoisomerases sensitizes yeast cells to DNA damage
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