DNA topoisomerase 1
Also known as: TOP1
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.
Classification
- Family (Pfam)
- PF14370 Topo_C_assoc, PF01028 Topoisom_I, PF02919 Topoisom_I_N
- InterPro
- DNA_brk_join_enz, DNA_topo_DNA_db_N_dom1, DNA_topo_DNA_db_N_dom2, TopoI, TopoI_C_dom, TopoI_cat_a-hlx-sub_euk, TopoI_cat_a/b-sub_euk, TopoI_cat_euk, TopoI_DNA-bd_euk, TopoI_DNA-bd_euk_N_sf, TopoI_euk, TopoIB_AS, Topoisomer_I_DNA-bd, Topoisomerase_IB
- Functional cluster
- DEAD-Box RNA Helicases & Biogenesis Factors
Experimental structures · PDB · 15
- 1A31 X-ray 2.10A
- 1A35 X-ray 2.50A
- 1A36 X-ray 2.80A
- 1EJ9 X-ray 2.60A
- 1K4S X-ray 3.20A
- 1K4T X-ray 2.10A
- 1LPQ X-ray 3.14A
- 1NH3 X-ray 3.10A
- 1R49 X-ray 3.13A
- 1RR8 X-ray 2.60A
- 1RRJ X-ray 2.30A
- 1SC7 X-ray 3.00A
- … and 3 more
A predicted model is available from AlphaFold.
Gene Ontology · 38
- GO:0005694 chromosome
- GO:0001651 dense fibrillar component
- GO:0001650 fibrillar center
- GO:0005730 nucleolus
- GO:0005654 nucleoplasm
- GO:0005634 nucleus
- GO:0000932 P-body
- GO:0043204 perikaryon
- GO:0032993 protein-DNA complex
- GO:0005524 ATP binding
- GO:0003682 chromatin binding
- GO:0031490 chromatin DNA binding
- GO:0003677 DNA binding
- GO:0008301 DNA binding, bending
- GO:0003917 DNA topoisomerase type I (single strand cut, ATP-independent) activity
- GO:0003690 double-stranded DNA binding
- GO:0140693 molecular condensate scaffold activity
- GO:0019904 protein domain specific binding
- GO:0004674 protein serine/threonine kinase activity
- GO:0044877 protein-containing complex binding
- GO:0003723 RNA binding
- GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding
- GO:0003697 single-stranded DNA binding
- GO:0097100 supercoiled DNA binding
- GO:0031100 animal organ regeneration
- GO:0071373 cellular response to luteinizing hormone stimulus
- GO:0006338 chromatin remodeling
- GO:0007059 chromosome segregation
- GO:0032922 circadian regulation of gene expression
- GO:0007623 circadian rhythm
- GO:0006260 DNA replication
- GO:0006265 DNA topological change
- GO:0012501 programmed cell death
- GO:0051591 response to cAMP
- GO:0010332 response to gamma radiation
- GO:0009266 response to temperature stimulus
- GO:0009410 response to xenobiotic stimulus
- GO:0009303 rRNA transcription
Drugs targeting this protein · 17
- GIMATECAN inhibitor
- CAMPTOTHECIN-20-O-PROPIONATE inhibitor
- TOPOTECAN HYDROCHLORIDE inhibitor
- EXATECAN inhibitor
- KARENITECIN inhibitor
- AFELETECAN stabiliser
- BECATECARIN inhibitor
- BELOTECAN inhibitor
- 9-AMINOCAMPTOTHECIN inhibitor
- DIFLOMOTECAN inhibitor
- IRINOTECAN HYDROCHLORIDE inhibitor
- AR-67 inhibitor
- EDOTECARIN inhibitor
- TLC-388 inhibitor
- IRINOTECAN SUCROSOFATE inhibitor
- RUBITECAN inhibitor
- 7-ETHYL-10-HYDROXYCAMPTOTHECIN inhibitor
Related proteins · sequence + function similarity
- DNA topoisomerase 1 1.00
- DNA topoisomerase 1 0.99
- DNA topoisomerase 1 0.99
- DNA topoisomerase 1 0.99
- DNA topoisomerase 1 0.93
- DNA topoisomerase 1 0.89
- DNA topoisomerase 1 0.86
- DNA topoisomerase 1 0.84
- DNA topoisomerase 1 0.83
- DNA topoisomerase 1 0.79
- DNA topoisomerase 1 0.74
- DNA topoisomerase 1 0.74
Co-cited proteins · studied together in the literature
- Large T antigen 1 shared papers
- Nuclear pore complex protein Nup98-Nup96 1 shared papers
- Dual specificity protein kinase CLK4 1 shared papers
- Dual specificity protein kinase CLK1 1 shared papers
- Dual specificity protein kinase CLK3 1 shared papers
- Tissue factor 1 shared papers
- Taperin 1 shared papers
- Dual specificity protein kinase CLK2 1 shared papers
- DNA topoisomerase 2-alpha 2 shared papers
- DNA repair protein Ku80 2 shared papers
- DNA repair protein Ku70 1 shared papers
- Serine/threonine-protein phosphatase PP1-alpha catalytic subunit 1 shared papers
Literature · 44 cited papers
- Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation. Nat. Struct. Mol. Biol. · 2017
- Identification of Novel Proteins Co-Purifying with Cockayne Syndrome Group B (CSB) Reveals Potential Roles for CSB in RNA Metabolism and Chromatin Dynamics. PLoS ONE · 2015
- SUMO-2 orchestrates chromatin modifiers in response to DNA damage. Cell Rep. · 2015
- System-wide analysis of SUMOylation dynamics in response to replication stress reveals novel small ubiquitin-like modified target proteins and acceptor lysines relevant for genome stability. Mol. Cell. Proteomics · 2015
- Uncovering global SUMOylation signaling networks in a site-specific manner. Nat. Struct. Mol. Biol. · 2014
- Mapping of SUMO sites and analysis of SUMOylation changes induced by external stimuli. Proc. Natl. Acad. Sci. U.S.A. · 2014
- An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
- Taperin (c9orf75), a mutated gene in nonsyndromic deafness, encodes a vertebrate specific, nuclear localized protein phosphatase one alpha (PP1alpha) docking protein. Biol. Open · 2012
- Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
- CK2-mediated hyperphosphorylation of topoisomerase I targets serine 506, enhances topoisomerase I-DNA Binding, and increases cellular camptothecin sensitivity. PLoS ONE · 2012
- Rhythmic binding of Topoisomerase I impacts on the transcription of Bmal1 and circadian period. Nucleic Acids Res. · 2012
- System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci. Signal. · 2011
- … and 32 more in the literature graph