Complex mechanisms of topoisomerase II poisons revealed by whole-genome analysis
Rattachement africain : cn. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Topoisomerase II (TOP2) represents a vital enzyme which functions by introducing transient DNA breaks to resolve topological issues in DNA and regulate gene expression. The potentially toxic nature of these DNA breaks made the drugs that stabilize them, TOP2 poisons, into highly successful anticancer agents, and research tools. However, despite decades-long widespread usage of these drugs, not much is known about differences in the genome-wide profiles of DNA breaks caused by them. Here, we generate high-resolution genome-wide maps of DNA breaks induced by seven different TOP2 poisons in a human cancer cell line using the SSiNGLe method developed by our group. We find multiple notable differences even between the drugs with highly similar chemical structures, indicating that each poison targets a specific subpopulation of catalytically engaged TOP2 enzymes bound to DNA. The preferential targeting observed may be partly explained by the distinct local sequence preferences identified for each TOP2 poison. However, our results also indicate that genomic context, chromatin environment, and the heterogeneity of TOP2 cleavage complexes likely contribute. Altogether, this study has potential significant implications for our understanding of the reasons behind the clinical differences among the drugs and the mechanisms of TOP2 function.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Complex mechanisms of topoisomerase II poisons revealed by whole-genome analysis
- Date Crossref
- 30/04/2026
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Huaqiao University pays non établi dans la noticeUniversité ou école supérieure
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First Affiliated Hospital of Xiamen University Department of Xiamen Cell Therapy Research Center pays non établi dans la noticeÉtablissement de santé
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Xiamen University pays non établi dans la noticeUniversité ou école supérieure
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School of Medicine Institute of Genomics pays non établi dans la noticeUniversité ou école supérieure
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School of Life Sciences State Key Laboratory of Cellular Stress Biology pays non établi dans la noticeUniversité ou école supérieure
Huaqiao University, Department of Xiamen Cell Therapy Research Center — First Affiliated Hospital of Xiamen University et Xiamen University, avec 2 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.