Literature summary for 5.6.2.1 extracted from

Ishikawa, T.; Krzysko, K.A.; Kowalska-Loth, B.; Skrajna, A.M.; Czubaty, A.; Girstun, A.; Cieplak, M.K.; Lesyng, B.; Staron, K.
Activities of topoisomerase I in its complex with SRSF1 (2012), Biochemistry, 51, 1803-1816.

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Cloned(Commentary)

Cloned (Comment)	Organism
recombinant His-tagged full-length enzyme and enzyme fragments expression in Saccharomyces cerevisiae	Homo sapiens

Inhibitors

Inhibitors	Comment	Organism	Structure
SR proteins	inhibition of DNA nicking activity by SR proteins. Inhibition of the DNA nicking activity of Topo I by SRSF1 depends on RNA recognition motifs joined by a spacer, Topo I enzyme inhibition by spacer mutants, overview	Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
additional information	Homo sapiens	human topoisomerase I is a dual-activity enzyme. First, it transiently nicks double-stranded DNA. Next, topo I is a kinase that phosphorylates SR proteins, essential splicing factors, and regulators of splicing composed of one or two RNA recognition motifs (RRMs) followed by the RS domain (RS) and containing numerous serine-arginine repeats. Topo I is one of several protein kinases that phosphorylate SR proteins, enzymes of both families, SRPK1 and CLK1	?	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	-	-	-

Purification (Commentary)

Purification (Comment)	Organism
recombinant His-tagged full-length enzyme and enzyme fragments from Saccharomyces cerevisiae by nickel affinity chromatography and cation exchange chromatography	Homo sapiens

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
additional information	human topoisomerase I is a dual-activity enzyme. First, it transiently nicks double-stranded DNA. Next, topo I is a kinase that phosphorylates SR proteins, essential splicing factors, and regulators of splicing composed of one or two RNA recognition motifs (RRMs) followed by the RS domain (RS) and containing numerous serine-arginine repeats. Topo I is one of several protein kinases that phosphorylate SR proteins, enzymes of both families, SRPK1 and CLK1	Homo sapiens	?	-	?

Subunits

Subunits	Comment	Organism
More	Topo I is a single polypeptide of 765 amino acid residues composed of four domains: N-terminal domain (residues 1-214), core domain (residues 215-635), linker domain (residues 636-712), and C-terminal domain (residues 713-765). The core domain is further divided into three subdomains that form two distinct lobes in the threedimensional structure of topo I: the cap, including subdomains I and II (residues 215-433), and subdomain III (residues 434-635). Interactions between N-terminal domain and other domains of topo I are different for the protein in a complex with either DNA or SRSF1	Homo sapiens

Synonyms

Synonyms	Comment	Organism
Topo I	-	Homo sapiens
Topoisomerase I	-	Homo sapiens

General Information

General Information	Comment	Organism
additional information	structure-function-relationship, overview. Topo I is one of several protein kinases that phosphorylate SR proteins, enzymes of both families, SRPK1 and CLK1. SRPK1 efficiently phosphorylates serine residues localized in the N-terminal fragment of RS in SRSF1,23,24 while CLK1 phosphorylates all serine residues in RS25 or serine residues in the C-terminal portion of RS in SRSF1 previously phosphorylated by SRPK1. Topoisomerase I interacts with kinase SRSF1, interaction analysis with wild-type and mutant Topo I and wild-type and mutant SrSF1 kinase, phosphorylation sites, modeling, overview. Interactions between N-terminal domain and other domains of topo I are different for the protein in a complex with either DNA or SRSF1	Homo sapiens
physiological function	human topoisomerase I shows transient nicking of double-stranded DNA. Because of this activity, topo I is a main nuclear swivelase responsible for relieving a torsional stress that appears in DNA during transcription, replication, and chromatin condensation. The activity is also used to remove ribonucleotides incorporated during DNA replication and not deleted by the repair system. Because of the kinase activity of topo I, it influences alternative splicing of several transcripts. Both DNA relaxation and phosphorylation activities of topo I are also cooperating in preventing a conflict between transcription and DNA replication. Both activities do not work at the same time: DNA, a substrate for DNA relaxation, inhibits the kinase reaction, whereas both a protein substrate for the kinase activity and ATP inhibit DNA nicking	Homo sapiens

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Release 2023.1 (January 2023)