How do drug-induced topoisomerase I-DNA lesions signal to the molecular interaction network that regulates cell cycle checkpoints, DNA replication, and DNA repair?

Cell Biochem Biophys. 2000;33(2):175-80. doi: 10.1385/CBB:33:2:175.


Recent results suggest that potentially lethal DNA lesions may result when replication forks encounter trapped topoisomerase-DNA complexes or some other types of DNA damage. Such events produce what are called replication-encounter lesions. These lesions have the characteristic that they may allow single stranded DNA-associated replication protein A (RPA) to become juxtaposed to dsDNA end-associated DNA-protein kinase. Our results suggest that DNA-protein kinases may then hyperphosphorylate the RPA2 subunit. We discuss a possible pathway by which hyperphosphorylation of RPA2 could lead to the release of active p53. This could constitute a pathway for signaling the presence of replication-encounter lesions to the p53-dependent cell cycle arrest and/or apoptosis initiator systems.

Publication types

  • Review

MeSH terms

  • Apoptosis
  • Camptothecin / pharmacology
  • Cell Cycle / physiology*
  • DNA / chemistry
  • DNA / drug effects
  • DNA / metabolism
  • DNA Damage*
  • DNA Repair*
  • DNA Replication*
  • DNA Topoisomerases, Type I / metabolism*
  • Humans
  • Replication Origin
  • Signal Transduction
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / metabolism


  • Tumor Suppressor Protein p53
  • DNA
  • DNA Topoisomerases, Type I
  • Camptothecin