ArticleThe Biochemical journal2008
Role of a tryptophan anchor in human topoisomerase I structure, function and inhibition.
Article in The Biochemical journal, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
- Arginine methylation of human DNA topoisomerase I by PRMT5 facilitates DNA relaxation.Nucleic acids research · 2026Article
- Targeting neddylation sensitizes colorectal cancer to topoisomerase I inhibitors by inactivating the DCAF13-CRL4 ubiquitin ligase complex.Nature communications · 2023Article
- Signal-induced enhancer activation requires Ku70 to read topoisomerase1-DNA covalent complexes.Nature structural & molecular biology · 2023Article
- PARylation prevents the proteasomal degradation of topoisomerase I DNA-protein crosslinks and induces their deubiquitylation.Nature communications · 2021Article
- A conserved SUMO pathway repairs topoisomerase DNA-protein cross-links by engaging ubiquitin-mediated proteasomal degradation.Science advances · 2020Article
- The Indenoisoquinoline LMP517: A Novel Antitumor Agent Targeting both TOP1 and TOP2.Molecular cancer therapeutics · 2020Article
- Topoisomerase IB: a relaxing enzyme for stressed DNA.Cancer drug resistance (Alhambra, Calif.) · 2020Review
- Swapping of The N-Terminal Domain of Human Topoisomerase 1B with the CorrespondingReports of biochemistry & molecular biology · 2020Article
- Poly(ADP-ribose) polymers regulate DNA topoisomerase I (Top1) nuclear dynamics and camptothecin sensitivity in living cells.Nucleic acids research · 2016Article
- Article
- DNA topoisomerase I domain interactions impact enzyme activity and sensitivity to camptothecin.The Journal of biological chemistry · 2015Article
- Sequence selectivity of the cleavage sites induced by topoisomerase I inhibitors: a molecular dynamics study.Nucleic acids research · 2013Article
- A kinetic clutch governs religation by type IB topoisomerases and determines camptothecin sensitivity.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Evaluation of two models for human topoisomerase I interaction with dsDNA and camptothecin derivatives.PloS one · 2011Article
- Adaptation of topoisomerase I paralogs to nuclear and mitochondrial DNA.Nucleic acids research · 2009Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Human Top1 (topoisomerase I) relaxes supercoiled DNA during cell division and transcription. Top1 is composed of 765 amino acids and contains an unstructured N-terminal domain of 200 amino acids, and a structured functional domain of 565 amino acids that binds and relaxes supercoiled DNA. In the present study we examined the region spanning the junction of the N-terminal domain and functional domain (junction region). Analysis of several published Top1 structures revealed that three tryptophan residues formed a network of aromatic stacking interactions and electrostatic interactions that anchored the N-terminus of the functional domain to sub-domains containing the nose cone and active site. Mutation of the three tryptophan residues (Trp(203)/Trp(205)/Trp(206)) to an alanine residue, either individually or together, in silico revealed that the individual tryptophan residue's contribution to the tryptophan 'anchor' was additive. When the three tryptophan residues were mutated to alanine in vitro, the resulting mutant Top1 differed from wild-type Top1 in that it lacked processivity, exhibited resistance to camptothecin and was inactivated by urea. The results indicated that the tryptophan anchor stabilized the N-terminus of the functional domain and prevented the loss of Top1 structure and function.
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