Hervé Jacquiau, J.D., Ph.D., M.Sc., D.E.A.
Hervé Jacquiau, Ph.D. is one of the authors of this article which discusses how Camptothecin (CPT) targets DNA topoisomerase I by reversibly stabilizing a covalent enzyme-DNA intermediate. The cytotoxic activity of the drug, however, is S-phase dependent and results from the collision of advancing replication forks with the ternary CPT-Top1-DNA complexes. The response of S-phase and DNA damage checkpoints to CPT-induced lesions is consistent with this cytotoxic mechanism. However, the molecular interactions required to elicit these cytotoxic lesions during S-phase and the nature of the lesion(s) induced remain largely unknown.
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