Topoisomerase I poisoning results in PARP-mediated replication fork reversal

  title={Topoisomerase I poisoning results in PARP-mediated replication fork reversal},
  author={Arnab Ray Chaudhuri and Yoshitami Hashimoto and Raquel Herrador and Kai John Neelsen and Daniele Fachinetti and Rodrigo Bermejo and Andrea Cocito and Vincenzo Costanzo and Massimo Lopes},
  journal={Nature Structural &Molecular Biology},
Topoisomerase I (Top1) releases torsional stress during DNA replication and transcription and is inhibited by camptothecin and camptothecin-derived cancer chemotherapeutics. Top1 inhibitor cytotoxicity is frequently linked to double-strand break (DSB) formation as a result of Top1 being trapped on a nicked DNA intermediate in replicating cells. Here we use yeast, mammalian cell lines and Xenopus laevis egg extracts to show that Top1 poisons rapidly induce replication-fork slowing and reversal… CONTINUE READING
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A genome - wide camptothecin sensitivity screen identifies a mammalian MMS 22 L - NFKBIL 2 complex required for genomic stability

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