Human DNA topoisomerase I: relaxation, roles, and damage control
| Autor: | John B. Leppard, James J. Champoux |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
DNA Replication
Models Molecular chemistry.chemical_classification DNA ligase DNA clamp Protein Conformation DNA damage DNA polymerase II Topoisomerase DNA replication Eukaryotic DNA replication Biology Models Biological Cell biology DNA Topoisomerases Type I Biochemistry chemistry Genetics biology.protein Humans DNA supercoil Genetics (clinical) DNA Damage |
| Zdroj: | Chromosoma. 114:75-85 |
| ISSN: | 1432-0886 0009-5915 |
| DOI: | 10.1007/s00412-005-0345-5 |
| Popis: | 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, re-ligation 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 re-ligation 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. |
| Databáze: | OpenAIRE |
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