topoisomerase-1 (TOP1)

Function

• conversion of one topological isomer of DNA to another
• catalyzes ATP-independent breakage of single-stranded DNA, followed by passage & rejoining
• transiently breaks a DNA strand & forms a covalent bond between the active-site Tyr & the 3'phosphate of the broken DNA strand; the strand is subsequently re-ligated by nucleophilic attack of the 5'hydroxyl on this phosphodiester bond
• under certain conditions, nucleophilic attack of the 5'hydroxyl does not occur & the topoisomerase 1 forms a stalled covalent complex with the DNA; efficient repair of these stalled complexes is facilitated by tyrosyl-DNA phosphodiesterase 1
• cofactor for activator-dependent transcription by RNA polymerase 2 (identical to transcriptional cofactor termed PC3)
• eukaryotic topoisomerase 1 & topoisomerase 1 can relax both negative & positive supercoils, whereas prokaryotic enzymes relax only negative supercoils
• specifically inhibited by camptothecin (CPT), a plant alkaloid with antitumor activity

Structure

• monomer
• belongs to the eukaryotic type I topoisomerase family

Pathology

• chromosomal translocation t(11;20)(p15;q11) involving TOP1 with NUP98 is found in a form of therapy-related myelodysplastic syndrome
• topoisomerase 1 acts as a positive regulator of RNA polymerase II transcriptional activity at pathogen- induced genes (see topoisomerase-1 inhibitor)

More general terms

• topoisomerase

Additional terms

• Scl-70 antigen
• tyrosyl-DNA phosphodiesterase 1; tyr-DNA phosphodiesterase 1 (TDP1)

Database

• UniProt: http://www.uniprot.org/uniprot/P11387.html
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:7150
• OMIM: https://mirror.omim.org/entry/126420