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Literature summary for 5.6.2.1 extracted from

  • Gentry, A.C.; Juul, S.; Veigaard, C.; Knudsen, B.R.; Osheroff, N.
    The geometry of DNA supercoils modulates the DNA cleavage activity of human topoisomerase I (2011), Nucleic Acids Res., 39, 1014-1022.
    View publication on PubMedView publication on EuropePMC

Application

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(Commentary)

Cloned (Comment) Organism
expression in Saccharaomyces cerevisiae top1 null strain RS190 Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
camptothecin
-
Homo sapiens
irinotecan
-
Homo sapiens
topotecan
-
Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Substrates and Products (Substrate)

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

Synonyms Comment Organism
Topoisomerase I
-
Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
assay at Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
8
-
assay at Homo sapiens

General Information

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