Overexpression of type I topoisomerases sensitizes yeast cells to DNA damage

DNA topoisomerases play essential roles in many DNA metabolic processes. It has been suggested that topoisomerases play an essential role in DNA repai r. Topoisomerases can introduce DNA damage upon exposure to drugs that stab ilize the covalent protein-DNA intermediate of the topoisomerase reaction. Lesions in DNA are also able to trap topoisomerase-DNA intermediates, sugge sting that topoisomerases have the potential to either assist in DNA repair by locating sites of damage or exacerbating DNA damage by generation of ad ditional damage at the site of a lesion. We have shown that overexpression of yeast topoisomerase I (TOP1) conferred hypersensitivity to methyl methan esulfonate and other DNA-damaging agents, whereas expression of a catalytic ally inactive enzyme did not. Overexpression of topoisomerase II did not ch ange the sensitivity of cells to these DNA-damaging agents, Yeast cells lac king 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 partic ipate in the repair of DNA damage in yeast cells. However, the enzyme has t he potential of exacerbating DNA damage by forming covalent DNA-protein com plexes at sites of DNA damage.