, Volume 114, Issue 2, pp 75–85 | Cite as

Human DNA topoisomerase I: relaxation, roles, and damage control

  • John B. Leppard
  • James J. ChampouxEmail author


Human DNA topoisomerase I is an essential enzyme involved in resolving the torsional stress associated with DNA replication, transcription, and chromatin condensation. The catalytic cycle of the enzyme consists of DNA cleavage to form a covalent enzyme–DNA intermediate, DNA relaxation, and finally, religation of the phosphate backbone to restore the continuity of the DNA. Structure/function studies have elucidated a flexible enzyme that relaxes DNA through coordinated, controlled movements of distinct enzyme domains. The cellular roles of topoisomerase I are apparent throughout the nucleus, but the concentration of processes acting on ribosomal DNA results in topoisomerase I accumulation in the nucleolus. Although the activity of topoisomerase I is required in these processes, the enzyme can also have a deleterious effect on cells. In the event that the final religation step of the reaction cycle is prevented, the covalent topoisomerase I–DNA intermediate becomes a toxic DNA lesion that must be repaired. The complexities of the relaxation reaction, the cellular roles, and the pathways that must exist to repair topoisomerase I-mediated DNA damage highlight the importance of continued study of this essential enzyme.


Camptothecin Replication Fork Fluorescence Recovery After Photobleaching rDNA Transcription Linker Domain 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We thank Sharon Schultz and Heidrun Interthal for insightful comments during the preparation of the manuscript. This work was supported by grants GM60330 and GM49156 from the National Institutes of Health.


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© Springer-Verlag 2005

Authors and Affiliations

  1. 1.Department of Microbiology, School of MedicineUniversity of WashingtonSeattleUSA

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