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Natural compounds found to inhibit DNA topoisomerase 1 and reduce DNA damage

Revealing new clues to curb DNA damage
Credit: Proceedings of the National Academy of Sciences (2025). DOI: 10.1073/pnas.2421167122

Researchers have identified two natural compounds, patulin and xestoquinol, as new inhibitors of the enzyme topoisomerase 1, a key element in the correct functioning of DNA. The finding, in the Proceedings of the National Academy of Sciences, opens new doors to understanding and treating diseases related to damage to genetic material.

The research team includes Andrés Aguilera's laboratory, in collaboration with that of Ralf Wellinger (both professors in the Department of Genetics at the University of Seville in CABIMER) and with PharmaMAR.

DNA topoisomerase 1 is an enzyme present in all organisms, essential for . Its function is based on two catalytic steps: firstly, it cuts and then relinks the DNA, thus relaxing the topological stress generated during replication and transcription; secondly, the inhibitors prevent the cuts in the DNA from being ligated, leaving them open. In this way, they act as topoisomerase poisons, and are used as .

However, reliable inhibitors of the first step, DNA cleavage, are not available, despite their potential in basic research and possible applications in medicine. According to this research, patulin and xestoquinol inhibit the first catalytic activity of topoisomerase I in vitro, in yeast and human cells.

More information: Emanuela Tumini et al, Patulin and Xestoquinol are inhibitors of DNA topoisomerase 1, Proceedings of the National Academy of Sciences (2025).

Provided by University of Seville

Citation: Natural compounds found to inhibit DNA topoisomerase 1 and reduce DNA damage (2025, April 29) retrieved 28 September 2025 from /news/2025-04-natural-compounds-inhibit-dna-topoisomerase.html
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