Literature summary for 5.6.2.1 extracted from

Di Felice, F.; Chiani, F.; Camilloni, G.
Nucleosomes represent a physical barrier for cleavage activity of DNA topoisomerase I in vivo (2008), Biochem. J., 409, 651-656.

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Inhibitors

Inhibitors	Comment	Organism	Structure
camptothecin	this drug inhibits the rejoining reaction of DNAtopoisomerase I thus creating, in the presence of a denaturing agent, single-strand breaks and behaving like a single-strand nuclease. In vivo induction of camptothecin-dependent DNA topoisomerase I cleavage sites. Cells are treated for cleavage-site induction. Three different aliquots are incubated with 50, 100 or 200 microM camptothecin for 2 min at room temperature (25°C)	Saccharomyces cerevisiae

Organism

Organism	UniProt	Comment	Textmining
Saccharomyces cerevisiae	-	-	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
(TTA)35	trinucleotide repeat (TTA)35 lying in the intergenic region of chromosome XIII of Saccharomyces cerevisiae, between the RPM2 (RNase P mitochondrial 2) and PRE8 genes. This sequence contains the structural elements suitable to be susceptible to DNA topoisomerase I site-specific activity and to assemble nucleosomes. DNA topoisomerase I strongly recognizes the TTA repeats. The (TTA)35 repeat is engaged in a positioned nucleosome in vivo. DNA topoisomerase I efficiently reacts with the TTA repeat, the (TTA)35 sequence, the longest and most stable among the simple repeated sequences in Saccharomyces cerevisiae, is organized in a positioned nucleosome and this can possibly account for its high stability, in fact each nucleosome stores one negative supercoil, thus preventing DNA denaturation and induction of conformational alterations responsible for genetic instability. DNA topoisomerase I in vivo cleaves the (TTA)35 sequence after nucleosome removal, the positioned nucleosome on the (TTA)35 sequence represents a hindrance to the DNA topoisomerase I activity. This last conclusion, based on the glucose/galactose experiments, represents the first formal evidence that DNA topoisomerase I cannot react with nucleosomal DNA	Saccharomyces cerevisiae	?	-	?

Synonyms

Synonyms	Comment	Organism
DNA topoisomerase I	-	Saccharomyces cerevisiae

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Release 2023.1 (January 2023)