Application | Comment | Organism |
---|---|---|
pharmacology | topoisomerase I is the target for camptothecin-based anticancer drugs that act by increasing levels of topoisomerase I-mediated DNA scission | Homo sapiens |
Cloned (Comment) | Organism |
---|---|
expression in Saccharaomyces cerevisiae top1 null strain RS190 | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
camptothecin | - |
Homo sapiens | |
irinotecan | - |
Homo sapiens | |
topotecan | - |
Homo sapiens |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
additional information | substrate is negatively and positively supercoiled pBR322 DNA. Topoisomerase I removes positive superhelical twists about 10fold faster than it does negative superhelical twists | Homo sapiens | ? | - |
? |
Synonyms | Comment | Organism |
---|---|---|
Topoisomerase I | - |
Homo sapiens |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
37 | - |
assay at | Homo sapiens |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
8 | - |
assay at | Homo sapiens |
General Information | Comment | Organism |
---|---|---|
additional information | intercalators enhance topoisomerase I-mediated cleavage of negatively supercoiled substrates but not positively supercoiled or linear DNA. These compounds act by altering the perceived topological state of the double helix, making underwound DNA appear to be overwound to the enzyme, acting like topological poisons of topoisomerase I | Homo sapiens |
physiological function | as a result of its catalytic mechanism, topoisomerase I plays an important role in removing positive DNA supercoils that accumulate ahead of replication forks and transcription complexes. Cleavage events most likely to generate permanent genomic damage are those that occur ahead of DNA tracking systems. The human enzyme maintains higher levels of cleavage with positively as opposed to negatively supercoiled substrates in the absence or presence of anticancer drugs. Sites of topoisomerase I-mediated DNA cleavage do not appear to be affected by supercoil geometry, but rates of ligation are slower with positively supercoiled substrates | Homo sapiens |