ArticleBiochemistry2005
Impact of the C-terminal domain of topoisomerase IIalpha on the DNA cleavage activity of the human enzyme.
Article in Biochemistry, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 49 citations in OpenAlex.
- Mutagenesis of Intrinsically Disordered Domain Impacts Topoisomerase IIα Catalytic Activity.International journal of molecular sciences · 2025Article
- ERK2-topoisomerase II regulatory axis is important for gene activation in immediate early genes.Nature communications · 2023Article
- Super-resolution microscopy reveals the number and distribution of topoisomerase IIα and CENH3 molecules within barley metaphase chromosomes.Chromosoma · 2023Article
- Recognition of DNA Supercoil Handedness during Catenation Catalyzed by Type II Topoisomerases.Biochemistry · 2022Article
- Exploration of the Role of the C-Terminal Domain of Human DNA Topoisomerase IIα in Catalytic Activity.ACS omega · 2021Article
- Mitotic chromosomes.Seminars in cell & developmental biology · 2021Review
- Structural basis for allosteric regulation of Human Topoisomerase IIα.Nature communications · 2021Article
- Role of Aurora B and Haspin kinases in the metaphase Topoisomerase II checkpoint.Cell cycle (Georgetown, Tex.) · 2021Review
- Molecular mechanisms of topoisomerase 2 DNA-protein crosslink resolution.Cellular and molecular life sciences : CMLS · 2020Review
- Article
- 6,6'-Dihydroxythiobinupharidine as a poison of human type II topoisomerases.Bioorganic & medicinal chemistry letters · 2019Article
- The Impact of the C-Terminal Region on the Interaction of Topoisomerase II Alpha with Mitotic Chromatin.International journal of molecular sciences · 2019Article
- Casein kinase II-dependent phosphorylation of DNA topoisomerase II suppresses the effect of a catalytic topo II inhibitor, ICRF-193, in fission yeast.The Journal of biological chemistry · 2019Article
- TOPII and chromosome movement help remove interlocks between entangled chromosomes during meiosis.The Journal of cell biology · 2018Article
- The Roles of DNA Topoisomerase IIβ in Transcription.International journal of molecular sciences · 2018Review
- Post-translational modifications in DNA topoisomerase 2α highlight the role of a eukaryote-specific residue in the ATPase domain.Scientific reports · 2018Article
- Non-Catalytic Roles of the Topoisomerase IIα C-Terminal Domain.International journal of molecular sciences · 2017Review
- Roles of the C-terminal domains of topoisomerase IIα and topoisomerase IIβ in regulation of the decatenation checkpoint.Nucleic acids research · 2017Article
- A noncatalytic function of the topoisomerase II CTD in Aurora B recruitment to inner centromeres during mitosis.The Journal of cell biology · 2016Article
- Effects of Olive Metabolites on DNA Cleavage Mediated by Human Type II Topoisomerases.Biochemistry · 2015Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The enzymatic function of the C-terminal domain of eukaryotic topoisomerase II is not well defined. This region of the enzyme is highly variable and hydrophilic and contains nuclear localization signals and phosphorylation sites. In contrast to eukaryotic topoisomerase II, type II enzymes from chlorella virus completely lack the C-terminal domain. These viral enzymes are characterized by a robust DNA cleavage activity, high coordination between their two active site tyrosyl residues, and reduced sensitivity to anticancer drugs. As a first step toward characterizing the contribution of the C-terminal domain of human topoisomerase IIalpha to enzyme function, the protein was truncated at amino acid 1175, which corresponds to the C-terminal residue of Paramecium bursaria chlorella virus-1 topoisomerase II as determined by BLAST sequence alignment. Although the overall catalytic activity of the resulting enzyme, hTop2alphaDelta1175, was lower than that of full-length topoisomerase IIalpha, the mutant protein displayed a double-stranded DNA cleavage activity that was approximately 2-3-fold higher. While the DNA breaks created by hTop2alphaDelta1175 were primarily double stranded, cuts generated by topoisomerase IIalpha were primarily single stranded. Thus, the enhanced cleavage observed for hTop2alphaDelta1175 appears to be due, at least in part, to an increase in active site coordination. Finally, hTop2alphaDelta1175 displayed a distinctly lower susceptibility to anticancer agents than did topoisomerase IIalpha, despite the fact that it showed a similar binding affinity for etoposide. Therefore, the C-terminal domain of human topoisomerase IIalpha appears to play significant roles in modulating the DNA cleavage/ligation reaction of the enzyme and its response to anticancer agents.
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