, Volume 114, Issue 2, pp 75–85

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


DOI: 10.1007/s00412-005-0345-5

Cite this article as:
Leppard, J.B. & Champoux, J.J. Chromosoma (2005) 114: 75. doi:10.1007/s00412-005-0345-5


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.

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

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

Personalised recommendations