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Our Research
• CPTs are DNA-Protein interface inhibitors that block topoI-mediated DNA re-ligation reactions. This leads to the formation of covalently-linked DNA-topoI complexes (topo1-CC) at the broken DNA strands and the collision of the replication forks lead to DNA–double strand breaks( DNA-DSB)
•In CPT-resistant cells, topoI is degraded rapidly and the broken end of the DNA is available for repair. In contrast, cells with slow topoI degradation fail to repair DNA-DSB, which ensures apoptosis.
• CPT-induced topoI degradation is mediated by the Ubiquitin proteasomal pathway (UPP), and the inhibition of this pathway overcomes drug resistance
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