ArticleNucleic acids research2006
The different cleavage DNA sequence specificity explains the camptothecin resistance of the human topoisomerase I Glu418Lys mutant.
Article in Nucleic acids research, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
10 citing papers in PubMed, 21 citations in OpenAlex.
- Parallel Genomic Alterations of Antigen and Payload Targets Mediate Polyclonal Acquired Clinical Resistance to Sacituzumab Govitecan in Triple-Negative Breast Cancer.Cancer discovery · 2021Article
- Natural Compounds as Therapeutic Agents: The Case of Human Topoisomerase IB.International journal of molecular sciences · 2021Review
- Swapping of The N-Terminal Domain of Human Topoisomerase 1B with the CorrespondingReports of biochemistry & molecular biology · 2020Article
- Topoisomerase IB: a relaxing enzyme for stressed DNA.Cancer drug resistance (Alhambra, Calif.) · 2020Review
- Molecular mechanism of the camptothecin resistance of Glu710Gly topoisomerase IB mutant analyzed in vitro and in silico.Molecular cancer · 2013Article
- Evidence of the crucial role of the linker domain on the catalytic activity of human topoisomerase I by experimental and simulative characterization of the Lys681Ala mutant.Nucleic acids research · 2009Article
- Topoisomerase I gene mutations at F270 in the large subunit and N184 in the small subunit contribute to the resistance mechanism of the unicellular parasite Leishmania donovani towards 3,3'-diindolylmethane.Antimicrobial agents and chemotherapy · 2009Article
- A single mutation in the 729 residue modulates human DNA topoisomerase IB DNA binding and drug resistance.Nucleic acids research · 2008Article
- Mutational study of the "catalytic tetrad" of DNA topoisomerase IB from the hemoflagellate Leishmania donovani: Role of Asp-353 and Asn-221 in camptothecin resistance.Biochemical pharmacology · 2008Article
- Mutation of Gly721 alters DNA topoisomerase I active site architecture and sensitivity to camptothecin.The Journal of biological chemistry · 2008Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Yeast cells expressing the Glu418Lys human topoisomerase I mutant display a camptothecin resistance that slowly decreases as a function of time. Molecular characterization of the single steps of the catalytic cycle of the purified mutant indicates that it has a relaxation activity identical to the wild-type protein but a different DNA sequence specificity for the cleavage sites when compared to the wild-type enzyme, as assayed on several substrates. In particular the mutant has a low specificity for CPT sensitive cleavable sites. In fact, the mutant has, at variance of the wild-type enzyme, a reduced preference for cleavage sites having a thymine base in position -1 of the scissile strand. This preference, together with the strict requirement for a thymine base in position -1 for an efficient camptothecin binding, explains the temporary camptothecin resistance of the yeast cell expressing the mutant and points out the importance of the DNA sequence in the binding of the camptothecin drug.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.