Recombinant Human DNA topoisomerase 1 (TOP1), partial

Function

Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(3'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 5'-OH DNA strand. The free DNA strand then rotates around the intact phosphodiester bond on the opposing strand, thus removing DNA supercoils. Finally, in the religation step, the DNA 5'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone (By similarity). Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells. Involved in the circadian transcription of the core circadian clock component BMAL1 by altering the chromatin structure around the ROR response elements (ROREs) on the BMAL1 promoter

Subcellular Location

Nucleus, nucleolus; Nucleus, nucleoplasm

Disease Association

[A chromosomal aberration involving TOP1 is found in a form of therapy-related myelodysplastic syndrome. Translocation t(11;20)(p15;q11) with NUP98]

Tissue Specificity

Endothelial cells

Subunit

(Microbial infection) Interacts with SV40 Large T antigen; this interactions allows viral DNA replication

• D'Arpa P. et al. cDNA cloning of human DNA topoisomerase I: catalytic activity of a 67.7-kDa carboxyl-terminal fragment. — Proc. Natl. Acad. Sci. U.S.A. (1988)
• Kunze N. et al. Structure of the human type I DNA topoisomerase gene. — J. Biol. Chem. (1991)
• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)
• Deloukas P. et al. The DNA sequence and comparative analysis of human chromosome 20. — Nature (2001)
• Mural R.J. et al. PubMed: CI-5GBD0VIIJ7C63 (SEP-)
• Kunze N. et al. Structural characterisation of the human DNA topoisomerase I gene promoter. — Eur. J. Biochem. (1990)
• Bienvenut W.V. et al. PubMed: CI-1MMBVPFO7979Q (DEC-)
• Fujimori A. et al. Mutation at the catalytic site of topoisomerase I in CEM/C2, a human leukemia cell line resistant to camptothecin. — Cancer Res. (1995)