Topoisomerase (DNA topoisomerases) is an enzyme that catalyzes the changes in the intertwined state of two DNA strands. Allan, J. M. & Travis, L. B. Mechanisms of therapy-related carcinogenesis. Thomas, A. Vanden Broeck, A. et al. Enzymes called helicases then separate the two strands of the double helix, exposing two template surfaces for the alignment of free nucleotides. Cell Cycle 18, 23772384 (2019). Dev. TOP1, TOP1MT, TOP2A and TOP2B bind double-stranded DNA; TOP3A and TOP3B bind single-stranded DNA or RNA. Proteome dynamics at broken replication forks reveal a distinct ATM-directed repair response suppressing DNA double-strand break ubiquitination. Sci. Signatures of TOP1 transcription-associated mutagenesis in cancer and germline. F1000Res. Piskadlo, E. & Oliveira, R. A. Mol. & Williams, R. S. Molecular mechanisms of topoisomerase 2 DNAprotein crosslink resolution. Centromeric and telomeric regions and ribosomal DNA appear to retain catenated segments until anaphase8. TOP2-DPCs can also be directly excised by endonucleases100,241,270 (Fig. Regairaz, M. et al. & Wang, J. C. DNA topoisomerase II and neural development. 1a). Structure-specific endonucleases Xpf and Mus81 play overlapping but essential roles in DNA repair by homologous recombination. Yet their association with chromatin remodelling complexes could contribute to DNA repair135,136,137. Proc. 73, 43624371 (2013). Schellenberg, M. J. et al. 19, 2765 (2018). Cell 170, 774786.e19 (2017). Processing of TOP2cc by proteolysis and tyrosyl-DNA phosphodiesterase 2 (TDP2) produce DSBs. Cell 47, 980986 (2012). Crit. Biochem. Topoisomerase is an enzyme that allows DNA to change its topology, which is its shape. J. Biol. Natl Acad. A critical role for the ubiquitin-conjugating enzyme Ubc13 in initiating homologous recombination. Ye, J. et al. PLoS Genet. Desai, S. D., Liu, L. F., Vazquez-Abad, D. & DArpa, P. Ubiquitin-dependent destruction of topoisomerase I is stimulated by the antitumor drug camptothecin. The role of topoisomerase II on breakage and proximity of RUNX1 to partner alleles RUNX1T1 and EVI1. Such chromatin loops generate DNA topological and torsional constraints, which are substrates for topoisomerases (Fig. Cell 25, 450465 (2020). In contrast to the dominant role for HDR in repairing TOP1-induced DSBs, NHEJ is preferentially used for TOP2-induced DSBs even in cycling cells222 (Fig. Libura, J., Slater, D. J., Felix, C. A. These drugs are classically used to map TOP2ccs and study their DNA damaging effects and repair pathways32,48,206,227,228,229,230. J. Mol. DSB end resection during HDR generates 3 single-strand tails, and thereby removes 5 blocking adducts such as TOP2-DPCs. Sci. & Roca, J. Topoisomerase II, not topoisomerase I, is the proficient relaxase of nucleosomal DNA. Indeed, TOP1 depletion increases R-loop abundance in heterochromatin domains of human HEK293 cells169 and at transcription termination sites of highly expressed genes in HeLa cells69. Pommier, Y., Leo, E., Zhang, H. & Marchand, C. DNA topoisomerases and their poisoning by anticancer and antibacterial drugs. 55, 509524 (2020). Herbaux, C. et al. To demonstrate that the BRCA1/BARD1complex assembles to chromatin . Beginning at the origin of replication, a complex Read More An RNA virus hijacks an incognito function of a DNA repair enzyme. This interaction can efficiently remove Sc+ and allow translocation of Pol II. Salceda, J., Fernandez, X. The accumulation of R-loops in the context of TOP1 deficiency is a potential source of DNA breaks and genomic instability72,73. Cell Biol. USA 97, 18851890 (2000). Cancer Res. Pommier, Y., Sun, Y., Huang, S. N. & Nitiss, J. L. Roles of eukaryotic topoisomerases in transcription, replication and genomic stability. 3h,i). Exp. Champoux, J. J. DNA topoisomerases: structure, function, and mechanism. Biophys. Natl Acad. As cancer survival statistics have improved, t-AML cases have increased; up to 15% of all acute myeloid leukaemia (AML) cases can be classified as t-AML289. Mol. Nature 434, 108113 (2005). 20, 48734881 (2014). USA 100, 52055210 (2003). Nat. Cell. Differential and common DNA repair pathways for topoisomerase I- and II-targeted drugs in a genetic DT40 repair cell screen panel. 8, 24992504 (2002). Transcriptional elongation requires DNA break-induced signalling. Studies with anticancer drugs that target TOPccs and with self-poisoning topoisomerases provide complementary approaches to elucidate the DNA damaging effects of trapped TOPccs and the repair pathways of and cellular responses to TOP1ccs31, TOP1MTccs202, TOP2ccs203,204 and TOP3Bccs2. N. Engl. The potential activity of TOP3A for removing hemicatenanes during replication in human cells needs to be further established. Annu. Potts, P. R., Porteus, M. H. & Yu, H. Human SMC5/6 complex promotes sister chromatid homologous recombination by recruiting the SMC1/3 cohesin complex to double-strand breaks. Biol. PubMed 71, 6981 (2018). Pol II, polymerase II. Zimmermann, M. et al. e | TOP3A in association with the Bloom syndrome protein (BLM)TOP3ARecQ-mediated genome instability proteins (RMI1/2) (BTR) dissolvasome complex (not shown) resolves DNA hemicatenanes arising during replication and recombination by passing a single strand of DNA through a break made in another DNA strand (single-strand passage)6,357. f | TOP3B is the only RNA-only topoisomerase14; it resolves intramolecular RNA intertwines (knots) by single-strand passage. Proc. Commun. Pouliot, J. J., Robertson, C. A. 60, 21692192 (2017). Analysis of t(15;17) chromosomal breakpoint sequences in therapy-related versus de novo acute promyelocytic leukemia: association of DNA breaks with specific DNA motifs at PML and RARA loci. Conversion of topoisomerase I cleavage complexes on the leading strand of ribosomal DNA into 5-phosphorylated DNA double-strand breaks by replication runoff. Defective DNA single-strand break repair in spinocerebellar ataxia with axonal neuropathy-1. What is the Difference Between Helicase and Topoisomerase 222, 2740 (2000). J. Biol. Nucleic Acids Res. PubMedGoogle Scholar. Sci. Davidson, I. F. & Peters, J. M. Genome folding through loop extrusion by SMC complexes. Mays, A. N. et al. Nat. Nat. Rev. Google Scholar. Cell Rep. 16, 368378 (2016). & Pommier, Y. 34, 12591269 (2015). 64, 104348 (2021). Topoisomerases and the regulation of neural function However, in multicellular life it is bundled in. J. Mol. Its classical form is homologous recombination and its common effector is RAD51. DNA Repair. Felix, C. A. In bacteria, DNA exists in a single circular chromosome. The translocase activity of PICH was recently reported to extrude Sc DNA loops, which are relaxed by TOP3A to provide Sc+ substrates for sister chromatid disjunction by TOP2A and for the rapid disjunction of sister centromeres at anaphase53. Mol. (NHEJ). Mol. Telomere length heterogeneity in ALT cells is maintained by PML-dependent localization of the BTR complex to telomeres. Such knots have been proposed to contribute to chromatin organization9,10 and recombination11 in yeast models. Dev. Rep. 8, 9272 (2018). Clin. Effects of uracil incorporation, DNA mismatches, and abasic sites on cleavage and religation activities of mammalian topoisomerase I. J. Biol. It has been proposed that cells possess a decatenation checkpoint that limits chromosomal instability and aneuploidy in response to TOP2A dysfunction8. Finally, the detailed location and roles of topoisomerases at centromeres and telomeres, and how topoisomerases are coordinated with chromatin remodelling factors and the architecture of chromatin and chromosomes, represent promising areas of investigation. Mauritzson, N. et al. Nat. Induction of reversible complexes between eukaryotic DNA topoisomerase I and DNA-containing oxidative base damages: 7,8-dihydro-8-oxoguanine and 5-hydroxycytosine. Target genes of topoisomerase II regulate neuronal survival and are defined by their chromatin state. "Topoisomerase is a class of enzymes that helps in winding and unwinding of DNA. Nature 590, 660665 (2021). Nucleic-acid excision pathways for TOP1 and/or TOP2 include excision by the endonucleases MRE11, CtIP and XPFERCC1, or excision by tyrosyl-DNA phosphodiesterase 1 (TDP1) and TDP2 (step 4). Deiss, K. et al. Schalbetter, S. A., Mansoubi, S., Chambers, A. L., Downs, J. & Osheroff, N. Topoisomerase II poisons: converting essential enzymes into molecular scissors. The removal of cohesin at prophase through the so-called prophase pathway is crucial for successful mitosis as condensins replace cohesins93. 91-92, 102849102849 (2020). & Shuman, S. Site-specific ribonuclease activity of eukaryotic DNA topoisomerase I. Mol. are supported by the Center for Cancer Research of the US National Cancer Institute (CCR-NCI) (Z01 BC 006161 and Z01 BC 006150 to Y.P.). Sim, S.-P. & Liu, L. F. Nucleolytic cleavage of the mixed lineage leukemia breakpoint cluster region during apoptosis. Natl Acad. Proc. 18, 45534559 (1990). Tewey, K. M., Chen, G. L., Nelson, E. M. & Liu, L. F. Intercalative antitumor drugs interfere with the breakage-reunion reaction of mammalian DNA topoisomerase II. Nat. Ahmad, M., Xu, D. & Wang, W. Type IA topoisomerases can be magicians for both DNA and RNA in all domains of life. Spartan deficiency causes accumulation of topoisomerase 1 cleavage complexes and tumorigenesis. Pourquier, P. et al. About Transcript DNA replication involves key enzymes like topoisomerase, helicase, DNA primase, DNA polymerase, and DNA ligase. During prophase, condensin is the primary driver of chromosome condensation as it scaffolds DNA loops (Fig. Their trapping by TOP2 poisons is the target of the anticancer drugs etoposide, doxorubicin, mitoxantrone and amsacrine (Supplementary Box 1), which generate TOP2-DPCs coupled with DSBs and SSBs. Blood 105, 21242131 (2005). Moreover, TOP2B binds to DSB sites163 and its activity at chromatin loops could serve to regulate DNA repair domains164. Three forms of DNA are most prevalent in nature: circular, linear and supercoiled." Circular DNA is covalently closed and does not have any interruption between nucleotides. USA 103, 89538958 (2006). Manthei, K. A. 42, 72597267 (2014). 276, 3159031595 (2001). Life 10, 164 (2020). 4c). Topoisomerase II contributes to DNA secondary structure-mediated double-stranded breaks. Endogenous DNA 3 blocks are vulnerabilities for BRCA1 and BRCA2 deficiency and are reversed by the APE2 nuclease. Polymerase extends the strands in the 5' to 3' direction, while ligase connects Okazaki fragments on the lagging strand. Cell Rep. 15, 988998 (2016). 6, 10191 (2015). Studies in mice with neuron-specific TOP1 inactivation demonstrate the crucial roles of TOP1 in postmitotic cells65. Mol. 1.21, bottom).Cleavage of the phosphodiester backbone in one segment of duplex DNA (termed the gate or G-segment) by the two active site tyrosines . Type II topoisomerases are topoisomerases that cut both strands of the DNA helix simultaneously in order to manage DNA tangles and supercoils. This article suggests the role of abortive TOP2ccs and defective repair as a source of prostate cancer. Commun. However, similar to the majority of mitochondrial proteins, they do not bear identifiable mitochondrial targeting sequences. Chem. 11, 2536 (2011). Quennet, V., Beucher, A., Barton, O., Takeda, S. & Lbrich, M. CtIP and MRN promote non-homologous end-joining of etoposide-induced DNA double-strand breaks in G1. 5a) can be initiated by ribonucleotides incorporated into the DNA by replicative polymerases148,218 (Fig. Krivtsov, A. V. et al. Post-translational modifications of topoisomerases such as phosphorylation133,140, oxidation141,142, acidification143 and acetylation133 could regulate the stability and reversibility of the TOPcc, and thus maintain such genomic anchor points. Sarni, D. et al. Proc. Yang, S.-W. et al. DNA Topoisomerase - an overview | ScienceDirect Topics 22, 27672772 (2008). Type II Topoisomerases. a | DPCs form either at 3 DNA ends (topoisomerase 1 (TOP1) or mitochondrial TOP1 (TOP1MT)) or 5 DNA ends (TOP2A, TOP2B, TOP3A or TOP3B). This work is a detailed review of SMC complexes. Mol. They comprise condensins, cohesins and the SMC5SMC6 complexes89,92,93,94. Transcription linked to recombination: a gene-internal promoter coincides with the recombination hot spot II of the human MLL gene. Natl Acad. and JavaScript. Biochemical Soc. 17, 207223 (2016). Recently, we showed that TOP3B-DPCs are also removed by the UPS pathway2. & Hammarsten, O. Transformation from committed progenitor to leukaemia stem cell initiated by MLL-AF9. Sci. Both TOP2B and TOP2A have been proposed to regulate the promoter-proximal pause and release of Pol II at immediate-early response genes84,85,86,87, as does TOP1 (ref.56). & Hsieh, T. S. DNA topoisomerase I is essential in Drosophila melanogaster. Biol. Due to the inaccessible location of the covalent tyrosylDNA bonds inside the TOPccs (Supplementary Fig. Maciejewski, S., Ullmer, W. & Semler, B. L. VPg unlinkase/TDP2 in cardiovirus infected cells: re-localization and proteolytic cleavage. (TADs). Mitochondrial protein-linked DNA breaks perturb mitochondrial gene transcription and trigger free radical-induced DNA damage. In addition to their role in organizing chromatin and chromosomes and minimizing DNA entanglements, topoisomerases associate with chromatin remodelling complexes. Notably, TOP3A acts independently of the BTR dissolvasome (as BLM, RMI1 and RMI2 do not enter mitochondria), which could imply that a mitochondrial helicase replaces the dissolvasome in working together with TOP3A. Nat. A transcript isoform of Topoisomerase biochemistry All topoisomerases act by cleaving and rejoining the nucleic acid backbone using a tyrosine nucleophilic residue (Supplementary Fig. CAS Hasan, S. K. et al. USA 109, 89898994 (2012). Lee, C. M., Wang, G., Pertsinidis, A. Smith, E. M., Lajoie, B. R., Jain, G. & Dekker, J. Invariant TAD boundaries constrain cell-type-specific looping interactions between promoters and distal elements around the CFTR locus. Natl Acad. & Roca, J. DNA knots occur in intracellular chromatin. Khiati, S. et al. Li, W. & Wang, J. C. Mammalian DNA topoisomerase III is essential in early embryogenesis. Non-SMC element 2 (NSMCE2) of the SMC5/6 complex helps to resolve topological stress. Detangling DNA replication | MIT News | Massachusetts Institute of Gomez-Herreros, F. et al. Navabpour, S., Rogers, J., McFadden, T. & Jarome, T. J. DNA double-strand breaks are a critical regulator of fear memory reconsolidation. Saha, S. et al. Proc. Open. Although GapR appears to be required for DNA replication, it's still not clear precisely how this protein promotes topoisomerase function to relieve supercoiling. Its main effectors are Ku70Ku80 and DNA-dependent protein kinase (DNA-PK). TOP2B: the first thirty years. Common fragile sites are characterized by faulty condensin loading after replication stress. Based on these data, a model was proposed in which TOP1 is recruited to promoters, but kept inactive until phosphorylation of Pol II CTD Ser2 by BRD4 releases Pol II and TOP1 from promoter-proximal pausing into productive transcript elongation56. Nature 551, 5156 (2017). & Nussenzweig, A. Endogenous DNA damage as a source of genomic instability in cancer. Recent analyses in human B cells show that more than 90% of TOP1-DPCs are removed during a 15-min repair time in wild type and TDP2/ cells, 70% in TDP1/ cells and only 40% in TDP1/TDP2/ cells253. A replication unit is any chunk of DNA that is capable of being replicated e.g. Sci. Yeast Top2 has also been shown to efficiently remove Sc+ in single-molecule model systems39, and yeast Top1 was shown to act at replication pause sites in ribosomal gene arrays40. Int. Commun. Estrogen induces mammary ductal dysplasia via the upregulation of myc expression in a DNA-repair-deficient condition. Biol. Adachi, Y., Luke, M. & Laemmli, U. K. Chromosome assembly in vitro: topoisomerase II is required for condensation. Topoisomerase- Definition, Types, Structure, Functions, Mechanism Berti, M. et al. Recurrent mutations in topoisomerase II cause a previously undescribed mutator phenotype in human cancers. DNA Repair. DNA breakage results, at least in part, from the formation of R-loops72,168. 36, 29072919 (2017). Sci. Crossovers of two strands of DNA originating from different DNA molecules. Lack of mitochondrial topoisomerase I (TOP1mt) impairs liver regeneration. Hudson, D. F. et al. Androgen-induced TOP2B-mediated double-strand breaks and prostate cancer gene rearrangements. Model for MLL translocations in therapy-related leukemia involving topoisomerase II-mediated DNA strand breaks and gene proximity. Jiang, W. et al. Res. Optimal function of the DNA repair enzyme TDP1 requires its phosphorylation by ATM and/or DNA-PK. This break-point clustering suggests that a specific mechanism is associated with therapy-related, but not de novo, AML translocations. 5b), and can produce large deletions and chromosomal translocations through non-homologous end joining (NHEJ)222,223,224,225,226 (Fig. Natl Acad. Natl Acad. J. Hum. Ishida, R. et al. Zhang, H. et al. & Machida, Y. J. DNAprotein crosslinks from environmental exposure: mechanisms of formation and repair. Zhang, Y. L. et al. Mapping topoisomerase sites in mitochondrial DNA with a poisonous mitochondrial topoisomerase I (Top1mt). Sci. Subsequently, a TOP1cc formed 5 adjacent to the ribonucleotide (possibly by the same TOP1 molecule sliding back on the DNA) (Fig. & Stasiak, A. Transcription-induced supercoiling as the driving force of chromatin loop extrusion during formation of TADs in interphase chromosomes. Chem. Nucleic Acids Res. Cell Biol. Austin, C. A. et al. USA 98, 1060810613 (2001). Rev. USA 93, 1153411539 (1996). Dual processing of R-loops and topoisomerase I induces transcription-dependent DNA double-strand breaks. Struct. Nucleic Acids Res. Although purifiedTDP2 protein has weak activity as a 3 TDP263,264, human TDP2 contributes to the removal of TOP1-DPCs in vivo. ATM specifically mediates repair of double-strand breaks with blocked DNA ends. Lee, S. K. & Wang, W. Roles of topoisomerases in heterochromatin, aging, and diseases. & Nash, H. A. & Ramadan, K. DNAprotein crosslink proteases in genome stability. Cline, S. D., Jones, W. R., Stone, M. P. & Osheroff, N. DNA abasic lesions in a different light: solution structure of an endogenous topoisomerase II poison. Breakage at the MLLAF9 or MLLAF4 fusion genes is associated with TOP2 cleavage sites99. Commun. USA 113, E55445551 (2016). Cancer Res. Natl Acad. Zhang, H., Meng, L. H., Zimonjic, D. B., Popescu, N. C. & Pommier, Y. Thirteen-exon-motif signature for vertebrate nuclear and mitochondrial type IB topoisomerases. 44, 28162826 (2016). TOP1 inhibition therapy protects against SARS-CoV-2-induced lethal inflammation. Hoa, N. N. et al. 22, 445464 (2021). Nat. g | TOP3B can also resolve RNA catenanes by single-strand passage197. Andersson, R. et al. Nucleic Acids Res. TOP3A, in addition to its roles in resolving double Holliday junctions and suppressing sister chromatid exchanges, is involved in DNA end resection160 and homology-directed repair (HDR)6,28,161,162. Zhang, H. et al. ATM may phosphorylate MRE11 and its cofactor, CtIP (also known as RBBP8), as these proteins are known to be phosphorylated by ATM and promote NHEJ of etoposide-induced TOP2-DPCs in G1 phase283. 24, 344352 (2017). Rev. EMBO J. & Pommier, Y. Debulking of topoisomerase DNAprotein crosslinks (TOP-DPC) by the proteasome, non-proteasomal and non-proteolytic pathways. Long, B. H., Musial, S. T. & Brattain, M. G. Single- and double-strand DNA breakage and repair in human lung adenocarcinoma cells exposed to etoposide and teniposide. & Austin, C. A. J. Google Scholar. Biol. Another mutagenic consequence of irreversible TOP1ccs results from their collisions with replication forks (Figs4c,6). Pardo, B., Moriel-Carretero, M., Vicat, T., Aguilera, A. In the meantime, to ensure continued support, we are displaying the site without styles Cohesins extrude chromatin into loops that are delineated by CCCTC-binding factor (CTCF) sites (Fig. Topoisomerase II-induced chromosome breakage and translocation is determined by chromosome architecture and transcriptional activity. Nat. Clin. Rev. This article provides an up-to-date review of TOP1 inhibitors approved and in clinical development for cancer treatments. 1. Chem. Cell Biol. Biol. Dev. Natl. However, rotation has been reported in yeast43,44 as replisomes converge or in mammalian cells at common fragile sites, which are chromosomal regions that are sensitive to replication stress and prone to DNA breaks45,46. Earnshaw, W. C., Halligan, B., Cooke, C. A., Heck, M. M. & Liu, L. F. Topoisomerase II is a structural component of mitotic chromosome scaffolds. 77, 8191 (2020). Betti, C. J. et al. 37, 738748 (2009). Mol. Kim, N. & Jinks-Robertson, S. The Top1 paradox: friend and foe of the eukaryotic genome. c | Differential roles of non-homologous end joining (NHEJ) and homology-directed repair (HDR) in repair of TOP1-induced single-ended DNA double-strand breaks (seDSBs) and TOP2-DPC-induced DSBs. Non-proteasomal proteolysis by SPRTN repairs replication-associated TOP1-DPCs and TOP2-DPCs245, and genetic inactivation of SPRTN causes RuijsAalfs syndrome with progeroid features and hepatocellular carcinomas245,247. Ataxia telangiectasia mutated activation by transcription- and topoisomerase I-induced DNA double-strand breaks. Zoghi, S. et al. The amount of DNA twist, which is the number of crossovers of the two strands across each other; writhe is a measure of the double helix winding around itself. 32, 271278 (2007). Cancer Res. Whereas DSB end resection by HDR efficiently removes TOP2-DPCs278, NHEJ can only ligate TOP2-DPCs after the removal of 5 TOP2 adducts, which restores the 3-OH and 5-phosphate ends279,280,281. Lieberman-Aiden, E. et al. Loop extrusion requires the ATPase activity and the translocation of cohesins, which stops upon cohesin encountering a CTCF protein bound to DNA in a convergent orientation98,99,100,101. Calderwood, S. K. A critical role for topoisomerase IIb and DNA double strand breaks in transcription. J. Biol. DNA gyrase is an essential bacterial enzyme that catalyzes the ATP-dependent negative super-coiling of double-stranded closed-circular DNA. Rev. A eukaryotic enzyme that can disjoin dead-end covalent complexes between DNA and type I topoisomerases. To obtain Proc. and A.N. Article 259, 1356013566 (1984). Referring to TDP1 and TDP2, enzymes that excise topoisomeraseDNA crosslinks by hydrolysing 3-phosphodiester and 5-phosphodiester bonds, respectively. Pourquier, P. et al. Duplex DNA and BLM regulate gate opening by the human TopoIII-RMI1-RMI2 complex. Mol. The mitochondrial isoform of topoisomerase 3A (TOP3A)186,368 is required at the end of replication to decatenate the daughter mtDNA molecules, which are intertwined across their OriH regions, a process that is facilitated by mitochondrial TOP1 (TOP1MT) and is independent of the usual TOP3A-interacting Bloom syndrome protein (BLM)TOP3ARecQ-mediated genome instability proteins (RMI1/2) (BTR) dissolvasome complex12. Unexpectedly, yeast Top1 (and Top2 when acting as a Top1 backup) enforces replication pausing by the topoisomerase 1-associated factor (Tof1) at replication fork barriers by binding to Tof1 and preventing head-on collisions between replication and transcription machineries40. Topoisomerases are needed to resolve the topological tensions arising during transcription. Britton, S. et al. & Marchand, C. Interfacial inhibitors: targeting macromolecular complexes. USA 84, 70247027 (1987). Chan, K. L., North, P. S. & Hickson, I. D. BLM is required for faithful chromosome segregation and its localization defines a class of ultrafine anaphase bridges. Chem. Natl Acad. Proc. Tdp1 processes chromate-induced single-strand DNA breaks that collapse replication forks. https://doi.org/10.1038/s41586-022-04403-y, DNA topoisomerase 1 represses HIV-1 promoter activity through its interaction with a guanine quadruplex present in the LTR sequence, Replication-associated formation and repair of human topoisomerase III cleavage complexes, Regulation of biological processes by intrinsically chiral engineered materials, Pectolinarigenin inhibits bladder urothelial carcinoma cell proliferation by regulating DNA damage/autophagy pathways, Super-resolution microscopy reveals the number and distribution of topoisomerase II and CENH3 molecules within barley metaphase chromosomes. Nat. Enforced cytokinesis without complete nuclear division in embryonic cells depleting the activity of DNA topoisomerase II. Genes Dev. Stigler, J., Camdere, G. O., Koshland, D. E. & Greene, E. C. Single-molecule imaging reveals a collapsed conformational state for DNA-bound cohesin. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Cell 69, 923.e6 (2018). Williams, J. S. et al. Huang, S. Y., Ghosh, S. & Pommier, Y. Topoisomerase I alone is sufficient to produce short DNA deletions and can also reverse nicks at ribonucleotide sites. 6b). Proc. The stability of TDP1 is regulated by the deubiquitylase UCHL3 (ref.265). Camptothecin generates DSBs in cycling cells when replication forks encounter TOP1-DPC (Figs4c,6c). Rev. Nat. Balmus, G. et al. Canela, A. et al. Pommier, Y., Nussenzweig, A., Takeda, S. et al. Natl Acad. Genetic studies show that TOP2 is required for chromosome condensation and segregation and for heterochromatin assembly in cell line models179. TRF2 and apollo cooperate with topoisomerase 2 to protect human telomeres from replicative damage. RNase H2-initiated ribonucleotide excision repair.
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