Affinage

TOP2A

DNA topoisomerase 2-alpha · UniProt P11388

Length
1531 aa
Mass
174.4 kDa
Annotated
2026-06-10
100 papers in source corpus 39 papers cited in narrative 39 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/9 claims corpus-supported (89%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TOP2A encodes a type II DNA topoisomerase that resolves DNA topological stress by forming transient enzyme-bridged double-strand breaks, and acts at replication forks, transcription units, and during chromosome condensation and segregation to safeguard genome integrity (PMID:17671091, PMID:27716481). At replication forks Top2 relieves torsional stress within a narrow window spanning the moving fork and acts coordinately with Top1, with double mutants showing fork block, checkpoint activation, and chromosome breakage (PMID:17671091); Top2 and the Sgs1-Top3 helicase pathway act redundantly to ensure fork merging and termination at rDNA barriers (PMID:26630413). Beyond swivel activity, TOP2 changes DNA catenation state to remodel chromatin, synergizing with the BAF (mSWI/SNF) complex to resolve facultative heterochromatin into accessible chromatin (PMID:28250416). During mitosis Top2 generates and later removes sister chromatid intertwines, with condensin biasing Top2 toward decatenation at anaphase and recruiting Top2 to chromosome arms following Polo kinase–driven condensin relocalization (PMID:27716481, PMID:26686624, PMID:21540296). The human enzyme is catalytically equivalent to TOP2B, so its isozyme-specific functions depend on extrinsic factors rather than intrinsic catalysis (PMID:8804406). TOP2A cleavage in human cells is enriched at CTCF-proximal and highly transcribed loci, scaling with gene length and transcript abundance, and these sites coincide with regions involved in TOP2-poison–related leukemic translocations (PMID:31649282, PMID:28385713). Therapeutic TOP2 poisons (etoposide, amsacrine, anthracyclines) trap covalent TOP2A-DNA cleavage complexes; resolution of these adducts requires proteolytic processing — proteasomal degradation gated by VCP/p97 and by ubiquitination via Bmi1/Ring1A — before TDP2 can remove the residual 5'-phosphotyrosyl adduct, and SUMOylation-dependent pathways (ZATT/ZNF451 with RAD54L2) provide a parallel proteasome-independent route (PMID:24808172, PMID:19956605, PMID:33941661, PMID:32587095, PMID:38055822, PMID:30011940). TOP2A protein abundance is set by competing ubiquitination and deubiquitination (PTEN/OTUD3, USP15, Rrp2) and by 3'-UTR translational control (HuR versus miR-548c-3p), linking enzyme levels to the G2 decatenation checkpoint, ultra-fine anaphase bridge formation, and an ATM-Chk2 abscission checkpoint during cytokinesis (PMID:33296677, PMID:21768308, PMID:26657567, PMID:28552615, PMID:37638884, PMID:36065190). TOP2A is also required for trophoblast and endometrial decidualization programs and for an EZH2/PRC2-H3K27me3 axis governing neurodevelopment (PMID:36585615, PMID:36417527, PMID:36138481).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1993 High

    Identifying the protein region that mediates drug sensitivity established that TOP2 is the physical target of anticancer poisons and localized the drug-interaction surface.

    Evidence purification and in vitro cleavage assays of the yeast top2-5 mutant enzyme with amsacrine and etoposide

    PMID:8395511

    Open questions at the time
    • Did not resolve atomic structure of the drug-binding pocket
    • Yeast enzyme, not human TOP2A
  2. 1995 High

    Mapping Ser741 as a shared quinolone/etoposide contact showed how single residues control ternary cleavage-complex stability and drug reversibility.

    Evidence site-directed mutagenesis and in vitro cleavage assays with etoposide and quinolone CP-115,953

    PMID:7657608

    Open questions at the time
    • Mechanism of complex irreversibility at the structural level unresolved
  3. 1996 High

    Cross-species complementation answered whether human TOP2A's specialized roles arise from catalysis itself, showing both human isoforms are catalytically interchangeable and isozyme specificity is extrinsic.

    Evidence complementation of yeast top2 mutants with human TOP2A and TOP2B constructs across multiple phenotypes

    PMID:8804406

    Open questions at the time
    • Did not identify the extrinsic factors conferring isozyme specificity
  4. 2006 High

    Demonstrating Tdp1 acts on 5'-phosphotyrosyl Top2 adducts opened the question of how covalent TOP2-DNA lesions are repaired.

    Evidence yeast deletion analysis plus in vitro biochemistry on Top2 peptide-DNA substrates and drug-sensitivity epistasis

    PMID:16751265

    Open questions at the time
    • Did not establish requirement for prior proteolytic processing
    • Relative contribution versus other phosphodiesterases unclear
  5. 2007 High

    Genomic mapping at replication forks defined where and when Top2 relieves torsional stress, establishing its coordinated action with Top1 to prevent fork-associated breakage.

    Evidence ChIP-on-chip of Top1/Top2 on replicating yeast chromosomes with top1/top2 epistasis and Rad53 checkpoint assays

    PMID:17671091

    Open questions at the time
    • Mechanism of sister chromatid junction accumulation not fully resolved
    • Yeast system
  6. 2009 High

    Linking Top2 occupancy to transcription-associated fragile loci and identifying Bmi1/Ring1A as the E3 ligase for drug-poisoned TOP2A connected enzyme localization and degradation to genome stability and drug efficacy.

    Evidence ChIP-chip of Top2/Hmo1 with γH2A mapping; siRNA screen plus in vitro ubiquitination and small-molecule ligase inhibition

    PMID:19737516 PMID:19956605

    Open questions at the time
    • Whether ubiquitination directly precedes TDP2 action not yet tested
    • Bmi1 substrate specificity for TOP2A versus other targets
  7. 2011 High

    Defining the HuR/miR-548c-3p competition at the 3'-UTR and the continuous mitotic requirement for Top2 established translational control of TOP2A abundance and its persistent role through telophase.

    Evidence RNA-IP, MS2-tagged RNA precipitation and reporter assays; yeast temperature-shift epistasis distinguishing Top2 from condensin

    PMID:21540296 PMID:21768308

    Open questions at the time
    • Medium confidence for the mitotic-timing finding
    • How translational control couples to cell-cycle demand unresolved
  8. 2014 High

    Showing irreversible Top2cc must be proteolytically processed before TDP2 can act, plus a TDP2 crystal structure, defined the ordered processing of trapped complexes and TDP2 substrate accommodation.

    Evidence in vitro Top2cc processing with suicide substrates, TDP2 enzymatic assays, and a 1.6 Å crystal structure

    PMID:24808172

    Open questions at the time
    • Identity of the in vivo protease(s) not defined here
    • Coupling to cellular degradation machinery unresolved
  9. 2015 High

    Identifying TOP2-BAF synergy, PTEN/OTUD3-mediated stabilization, Top2/Sgs1-Top3 redundancy, and TDP1 involvement broadened TOP2A function from torsional relief to catenation-based chromatin remodeling, checkpoint control, and break repair.

    Evidence genome-wide ATAC-seq with inhibitors; PTEN/TOP2A co-IP and decatenation checkpoint assays; yeast 2D-gel epistasis; TDP1 knockdown with cytogenetics

    PMID:26421495 PMID:26630413 PMID:26657567 PMID:28250416

    Open questions at the time
    • PTEN/OTUD3 and TDP1 findings are Medium confidence and lack in vitro reconstitution
    • Mechanism by which catenation state distinguishes heterochromatin from open chromatin unresolved
  10. 2016 High

    Demonstrating replication-independent formation and condensin-biased anaphase removal of sister chromatid intertwines resolved how Top2 toggles between concatenation and decatenation during the cell cycle.

    Evidence yeast genetics, 2D gels for SCIs, and condensin/Top2 conditional mutants across cell-cycle stages

    PMID:27716481

    Open questions at the time
    • Molecular signal that biases Top2 toward decatenation not fully defined
    • Yeast system
  11. 2017 High

    Single-base cleavage mapping, G4-ligand and CX-5461 cytotoxicity dependence, and Rrp2-mediated protection against SUMO-dependent degradation linked TOP2A genomic targeting and stability to drug responses and concealed-break exposure.

    Evidence genome-wide cleavage sequencing in K562; unbiased genetic screens with G4 ligands; CRISPR/deletion screen with SUMO-binding biochemistry in fission yeast

    PMID:28385713 PMID:28552615 PMID:34180392

    Open questions at the time
    • Determinants of CTCF-proximal versus transcription-proximal cleavage partitioning unresolved
    • Human ortholog of Rrp2 function not established here
  12. 2018 High

    Showing TDP2 cannot act on intact Top2ccs and identifying a dominant-negative TOP2A/90 isoform clarified that processing precedes TDP2 and that splice isoforms drive chemoresistance.

    Evidence TARDIS assays with TDP2 knockdown; co-IP and bidirectional gain/loss of function for TOP2α/90

    PMID:29514855 PMID:30011940

    Open questions at the time
    • TDP2-processing finding is Medium confidence
    • Physiological abundance and regulation of TOP2α/90 isoform unclear
  13. 2019 High

    Defining MDM4 binding and CTCF/transcription-proximal cleavage distribution connected TOP2A to p53 regulation and refined its genomic break landscape relative to chromatin features.

    Evidence co-IP with domain mapping and p53 activity assays; strand-specific nucleotide-resolution cleavage mapping in yeast and human

    PMID:30672125 PMID:31649282

    Open questions at the time
    • MDM4 finding is Medium confidence with no in vitro reconstitution
    • Functional consequence of SSB-prone sites in vivo not fully defined
  14. 2020 High

    Establishing the ZATT-TOP2A-PICH fork-reversal axis, ubiquitin-required adduct liberation, anthracycline poison-to-inhibitor switching, and TOP2α-dependent T cell apoptosis integrated TOP2A SUMOylation, ubiquitination, and drug pharmacology into genome-protective and pathological pathways.

    Evidence co-IP, PLA, fork-reversal EM and SUMOylation assays; TARDIS with ubiquitin-activating enzyme inhibitors; in vitro cleavage with isoform-specific iPSC-cardiomyocyte assays; enzymatic activity and apoptosis assays in primary T cells

    PMID:31399497 PMID:32193368 PMID:32587095 PMID:33296677

    Open questions at the time
    • Ubiquitination and T-cell findings are Medium confidence
    • How SUMOylation status routes between PICH recruitment and degradation unresolved
  15. 2021 Medium

    Identifying VCP/p97 as required for proteasomal degradation of trapped complexes placed an AAA-ATPase upstream of break exposure in adduct resolution.

    Evidence TARDIS assays with VCP/p97 inhibition, proteasome epistasis, and γH2AX readout

    PMID:33941661

    Open questions at the time
    • Single-lab study without reconstitution
    • How VCP/p97 recognizes TOP2-DNA adducts not defined
  16. 2022 Medium

    Establishing TOP2A requirements in trophoblast, decidualization, neurodevelopment, and its E2F1/EZH2/USP15 regulatory wiring extended TOP2A function to developmental programs and tissue-specific transcriptional control.

    Evidence shRNA knockdown with pathway profiling and embryo/mouse models; ChIP and reporter assays for E2F1; zebrafish/mouse behavior with H3K27me3 ChIP; co-IP with USP15-dependent stability assays

    PMID:36065190 PMID:36138481 PMID:36417527 PMID:36550695 PMID:36585615

    Open questions at the time
    • All findings Medium confidence in single labs
    • Whether developmental phenotypes reflect catalytic topoisomerase activity or non-catalytic roles is unresolved
  17. 2023 Medium

    Defining a cytokinetic abscission checkpoint driven by Top2cc degradation, RAD54L2-mediated SUMO-dependent resolution, and an EZH2/miR-139-5p axis connected TOP2A adduct handling to mitotic checkpoint signaling and tumor proliferation.

    Evidence live imaging and IF for the Rad17-MRN-ATM-Chk2-INCENP pathway; co-IP/ATPase and TDP2/ZATT epistasis for RAD54L2; ChIP, reporter, and senescence/xenograft assays for EZH2/miR-139-5p

    PMID:37638884 PMID:38008711 PMID:38055822

    Open questions at the time
    • RAD54L2 and EZH2 findings are Medium confidence
    • Relationship between TDP2-independent and TDP2-dependent resolution pathways in vivo not resolved
  18. 2024 Medium

    Identifying TOP2α-dependent rDNA-promoter damage from CX-5461 and a KDM5B/ZBTB16 axis controlling TOP2A in chemoresistance extended TOP2A targeting and regulation to nucleolar damage and epigenetic drug-resistance circuits.

    Evidence RADAR/Top2cc assays with genetic dependency in Eµ-Myc lymphoma; ChIP for H3K4me3 with USP7 ubiquitination and cisplatin sensitivity assays

    PMID:38287116 PMID:39062087

    Open questions at the time
    • Both findings Medium confidence in single labs
    • Generality of rDNA-localized TOP2α damage across cell types unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved which proteases and how the choice between proteasomal versus SUMO-dependent (ZATT/RAD54L2) resolution routes is made for trapped TOP2A-DNA complexes, and what extrinsic factors confer TOP2A isozyme specificity in human cells.
  • In vivo protease(s) for Top2cc processing unidentified
  • Determinants routing SUMOylated TOP2A to PICH recruitment versus degradation undefined
  • Extrinsic isozyme-specificity factors not identified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140097 catalytic activity, acting on DNA 4 GO:0003677 DNA binding 3 GO:0016853 isomerase activity 2
Localization
GO:0005634 nucleus 4 GO:0005694 chromosome 3 GO:0005730 nucleolus 1
Pathway
R-HSA-73894 DNA Repair 4 R-HSA-1640170 Cell Cycle 3 R-HSA-1643685 Disease 3 R-HSA-69306 DNA Replication 3 R-HSA-4839726 Chromatin organization 2
Partners
GINS1MDM4OTUD3PICHPTENRAD54L2TDP2ZATT

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 Top2 acts within a ~600 bp region spanning moving replication forks to counteract torsional stress; top2 single mutants accumulate sister chromatid junctions in S phase and activate the Rad53 checkpoint at M-G1 transition; top1 top2 double mutants exhibit fork block, DNA damage checkpoint activation, and chromosome breakage, showing coordinated action of Top1 and Top2 at replication forks. ChIP-on-chip mapping of Top1/Top2 on replicating yeast chromosomes; genetic analysis of top1, top2, and top1 top2 double mutants; checkpoint kinase (Rad53) phosphorylation assays; Exo1 epistasis experiments Genes & development High 17671091
2006 Tyrosyl-DNA phosphodiesterase (Tdp1) participates in repair of Top2-mediated DNA damage: Tdp1 can remove a Top2-derived peptide covalently linked to DNA via a 5'-phosphotyrosyl bond in vitro; tdp1 deletion confers hypersensitivity to Top2-targeting drugs; Tdp1 acts in collaboration with NHEJ, excision repair, and post-replication repair pathways. Yeast genetic deletion analysis; in vitro biochemical assay with bacterially expressed Tdp1p acting on 5'-phosphotyrosyl-linked Top2 peptide-DNA substrate; drug sensitivity assays; double-mutant epistasis Proceedings of the National Academy of Sciences of the United States of America High 16751265
2014 Irreversible Top2-DNA covalent complexes (Top2cc) require proteolytic processing (proteasomal degradation or denaturation) before TDP2 can remove the remaining 5'-phosphotyrosyl adduct; TDP2 is most active when the tyrosyl-linked DNA is single-stranded; TDP2 can also process tyrosine linked to RNA substrates. A 1.6 Å crystal structure of TDP2 bound to a 5'-ribonucleotide-bearing substrate explains RNA accommodation in the active site. In vitro TOP2cc processing assays with suicidal substrates; TDP2 enzymatic assays with varied substrates; crystal structure at 1.6 Å resolution; protease/denaturation pre-treatment experiments The Journal of biological chemistry High 24808172
2009 Top2 binds intergenic regions near transcribed genes specifically in S phase; Top2-bound loci exhibit low nucleosome density; loss of Top2 causes γH2A accumulation at these loci; HMG protein Hmo1 co-occupies these loci and is deleterious in top2 mutants. Top2 is dispensable for transcription per se but suppresses chromosome fragility at M-G1 transition at transcription-associated loci. ChIP-chip mapping of Top2 and Hmo1 across yeast cell cycle; γH2A ChIP; genetic analysis of top2 and hmo1 mutants; nucleosome occupancy assays Cell High 19737516
2009 Drug-poisoned TOP2α undergoes proteasomal degradation; the E3 ubiquitin ligase Bmi1/Ring1A ubiquitinates TOP2α in vitro and in cells; siRNA silencing of Bmi1 inhibits drug-induced TOP2α degradation and increases TOP2α-DNA cleavage complex persistence and drug efficacy. A small-molecule inhibitor of Bmi1/Ring1A ubiquitination activity prevents TOP2α ubiquitination and drug-induced degradation, synergistically enhancing TOP2 poison efficacy. siRNA screen identifying Bmi1/Ring1A; in vitro ubiquitination assay; cellular overexpression of Bmi1; drug sensitivity assays; small-molecule inhibitor of ubiquitin ligase PloS one High 19956605
2015 TOP2 (but not TOP1) synergizes with BAF (mSWI/SNF) ATP-dependent chromatin remodeling complexes genome-wide to resolve facultative heterochromatin to accessible chromatin, independent of transcription; this indicates that DNA decatenation/catenation topology changes (not torsional swiveling) are required for heterochromatin resolution. TOP2 also plays a role in re-formation of facultative heterochromatin, suggesting heterochromatin and accessible chromatin differ in catenation states. Genome-wide ATAC-seq and chromatin accessibility assays; TOP2 and TOP1 inhibitor treatments; BAF complex genetic perturbations; in vivo chromatin remodeling assays Nature structural & molecular biology High 28250416
2019 TOP2A cleavage activity in humans is distributed in two fractions: tightly localized CTCF-proximal sites and broadly distributed transcription-proximal sites (correlated with gene length and transcript abundance); single-nucleotide mapping distinguishes canonical DSB sites from strand-biased SSB-prone sites induced by etoposide; Mre11-dependent repair of Top2 breaks was characterized in yeast. Strand-specific nucleotide-resolution mapping of Top2 DNA cleavage (END-seq derivative) in S. cerevisiae and human genomes; comparison with ENCODE chromatin marks; etoposide treatment; meiotic Spo11 validation Nature communications High 31649282
2020 Upon replication stress, TOP2A is recruited to stalled replication forks in a manner dependent on HLTF, ZRANB3, and SMARCAL1; TOP2A undergoes SUMOylation mediated by the SUMO E3 ligase ZATT; SUMOylated TOP2A then recruits the SUMO-targeted DNA translocase PICH; this ZATT-TOP2A-PICH axis drives extensive fork reversal by resolving topological barriers. Loss of this axis causes accumulation of partially reversed forks and genome instability. Co-immunoprecipitation; proximity ligation assays; siRNA knockdown of HLTF/ZRANB3/SMARCAL1/ZATT/PICH; fork reversal electron microscopy; SUMOylation assays; genome instability measurements Molecular cell High 33296677
2011 HuR binds the TOP2A 3'-UTR and increases TOP2A translation; reducing HuR triggers recruitment of TOP2A mRNA to RISC components and cytoplasmic processing bodies; miR-548c-3p, identified by MS2-tagged RNA precipitation, mediates repression of TOP2A translation by antagonizing HuR; lowering TOP2A by HuR silencing or miR-548c-3p overexpression decreases DNA damage after doxorubicin treatment. RNA-binding protein immunoprecipitation; MS2-tagged RNA precipitation to identify miR-548c-3p; reporter assays; siRNA knockdown of HuR; miRNA overexpression; doxorubicin cytotoxicity assays Molecular and cellular biology High 21768308
2015 PTEN physically associates with TOP2A and stabilizes it through the deubiquitinase OTUD3; in PTEN-deficient cells, TOP2A ubiquitination increases and TOP2A protein levels decrease, leading to defective DNA decatenation checkpoint in G2, accumulation of ultra-fine anaphase bridges, and incomplete DNA decatenation. Co-immunoprecipitation of PTEN and TOP2A; ubiquitination assays; OTUD3 knockdown; analysis of ultra-fine bridges; decatenation checkpoint assays in PTEN-null cells Scientific reports Medium 26657567
2019 MDM4 and TOP2A physically bind each other; the C-terminal region (CTR) of TOP2A binds residues 188–238 of MDM4; this interaction stabilizes TOP2A protein post-translationally, and TOP2A binding activates MDM4 for p53 binding, resulting in enhanced p53 inhibition and increased cancer cell proliferation. Co-immunoprecipitation; domain-mapping experiments with truncation constructs; siRNA knockdown; cell proliferation assays; p53 activity assays Molecular oncology Medium 30672125
2017 TOP2 activity and transcription both contribute to DNA double-strand break formation after G4 ligand (pyridostatin and CX-5461) treatment; TOP2A was identified as a major effector of cytotoxicity by an unbiased genetic approach; TOP1 counteracts clastogenic activity of G4 ligands by limiting co-transcriptional G4 formation. Unbiased genetic screen; TOP2 inhibitor treatments; transcription inhibitor experiments; DSB detection assays eLife High 34180392
2017 TOP2A DNA cleavage in human cells is enriched at highly transcribed loci and genes involved in TOP2 poison-related leukemic translocations; TOP2A cleavage cluster regions (CCRs) occur in introns and lincRNA loci and are biased toward distal gene bodies; TOP2 poisons cause a proximal shift in CCR distribution; cleavage correlates independently with both gene length and transcript abundance. High-throughput sequencing of TOP2A cleavage sites at single-base precision in K562 cells; comparison with ENCODE data for transcription and open chromatin marks; etoposide and other TOP2 poison treatments Genome research High 28385713
2016 Sister chromatid intertwines (SCIs/catenanes) are formed independently of DNA replication during G2/M by Top2-dependent concatenation of cohesed chromatids due to physical proximity; condensin provides a bias in Top2 function toward decatenation at anaphase onset, as SCI removal in anaphase requires condensin and coincides with hyperactivation of condensin DNA supercoiling activity. Yeast genetic analysis; 2D gel electrophoresis for SCI detection; condensin and Top2 conditional mutants; cell cycle staging Molecular cell High 27716481
2015 Condensin relocalization from centromeres to chromosome arms during anaphase requires Polo kinase activity and is followed by Top2 recruitment to chromosome arms in a condensin-dependent manner; this Top2 recruitment coincides with condensin's DNA overwinding activity and promotes chromosome segregation. ChIP-seq of condensin and Top2 through the cell cycle; conditional Polo kinase inhibition; yeast cell biology with live imaging Cell reports Medium 26686624
2011 In fission yeast, Top2 is required continuously throughout mitosis including telophase for mitotic chromosome structure; condensin and Top2 have distinct requirements during mitosis—condensin SMC2 mutants accumulate telomeric DNA in lumps at telophase, whereas Top2 mutants show distinct chromosome segregation defects. Temperature-shift experiments with top2 temperature-sensitive and nda3 cold-sensitive double mutants; cell cycle staging; genetic epistasis Journal of cell science Medium 21540296
1996 Human TOP2α and TOP2β can each functionally substitute for yeast Top2 in chromosome segregation, vegetative growth, meiosis, and suppression of rDNA hyper-recombination, demonstrating that isozyme-specific roles of TOP2α in human cells depend on factors extrinsic to catalytic activity. Complementation of yeast top2 temperature-sensitive and disruption mutants with human TOP2α and TOP2β expression constructs; spore viability; rDNA recombination assays Molecular & general genetics : MGG High 8804406
1993 The top2-5 yeast mutant carrying clustered amino acid substitutions encodes a TOP2 enzyme with reduced amsacrine-stabilized and etoposide-stabilized cleavage in vitro; the mutations identify a domain of the topoisomerase II protein important for interaction with anti-TOP2 anticancer drugs. Purification of recombinant top2-5 protein; in vitro DNA cleavage assays with amsacrine and etoposide; sequencing of the top2-5 allele; yeast drug sensitivity assays The Journal of biological chemistry High 8395511
1995 Ser741 of yeast Top2 (homologous to Ser83 of E. coli GyrA) is near a binding site for both quinolone and etoposide; the Ser741→Trp mutation confers quinolone resistance and etoposide hypersensitivity by forming a more stable ternary etoposide-DNA-enzyme complex that is not readily reversible by heat. Site-directed mutagenesis; purification of mutant Top2 proteins; in vitro DNA cleavage assays with etoposide and quinolone CP-115,953; drug sensitivity assays in yeast The Journal of biological chemistry High 7657608
2008 Top2 mutants at Pro473 and Gly737 exhibit hypersensitivity to mAMSA; Pro473→Leu generates elevated Top2-mediated single-strand breaks but not double-strand breaks in vitro, and expression of an allele that can only generate single-strand breaks confers mAMSA hypersensitivity in yeast, demonstrating that Top2-generated single-strand breaks can be a component of cell killing. Mutagenesis screen; purification of mutant Top2 proteins; in vitro DSB and SSB cleavage assays; allele-specific expression in yeast; drug sensitivity assays The Journal of biological chemistry High 18723844
2018 A C-terminally truncated 90-kDa isoform of TOP2α (TOP2α/90), product of intron-19-retaining mRNA, heterodimerizes with full-length TOP2α/170; forced expression of TOP2α/90 in K562 cells suppresses etoposide-mediated DNA strand breaks and cytotoxicity, while siRNA knockdown of TOP2α/90 in resistant cells enhances etoposide-induced DSBs, establishing a dominant-negative mechanism of chemoresistance through heterodimerization. Co-immunoprecipitation of endogenous TOP2α/90 and TOP2α/170; forced expression and siRNA knockdown; DNA strand break assays; clonogenic survival assays; qPCR and immunoblotting Molecular pharmacology High 29514855
2020 Anthracyclines (doxorubicin, epirubicin) and mitoxantrone act as TOP2 poisons at low concentrations but attenuate TOP2-DNA covalent complex formation at higher concentrations, effectively becoming TOP2 inhibitors; TOP2B is the only TOP2 isoform present in iPSC-derived human cardiomyocytes, and doxorubicin does not detectably induce TOP2-DNA complexes in these cells, suggesting inhibition (not poisoning) of TOP2B may underlie cardiotoxicity. TOP2-DNA complex immunoassays in cells; in vitro DNA cleavage assays with doxorubicin, epirubicin, mitoxantrone, etoposide; iPSC-derived cardiomyocyte immunofluorescence; isoform-specific antibodies Molecular pharmacology High 31399497
2017 Fission yeast Rrp2, an Snf2-family SUMO-targeted DNA translocase, prevents excessive SUMOylation-dependent ubiquitination and proteasomal degradation of Top2; loss of Rrp2 increases Top2 degradation and exposes concealed DNA breaks at Top2-DNA complex sites; Rrp2 competes with the STUbL for SUMO chain binding and displaces SUMOylated Top2 from DNA. The budding yeast homolog Uls1 plays a similar role. Genome-wide CRISPR/deletion screen; Top2 SUMOylation and ubiquitination assays; Top2 protein stability measurements; DNA damage assays; biochemical SUMO-binding studies Molecular cell High 28552615
2021 VCP/p97 AAA ATPase is required for proteasomal degradation of etoposide-induced TOP2A- and TOP2B-DNA covalent complexes; VCP/p97 inhibition leads to prolonged accumulation of TOP2-DNA complexes in a manner epistatic with the proteasomal pathway and reduces etoposide-induced γH2AX phosphorylation, indicating fewer DSBs are exposed. TARDIS assay for TOP2-DNA complex quantification; VCP/p97 pharmacological inhibition; epistasis with proteasome inhibitors; γH2AX immunofluorescence Molecular pharmacology Medium 33941661
2020 Ubiquitin-activating enzyme inhibitors reduce processing of etoposide-induced TOP2A- and TOP2B-DNA covalent complexes; TOP2-DNA complexes are directly conjugated to ubiquitin; inhibition of the Bmi1/Ring1A ubiquitin ligase synergistically enhances TOP2 poison efficacy, establishing ubiquitination as a required step for liberation of protein-free DSBs from TOP2-DNA adducts. TARDIS assay; ubiquitin-activating enzyme inhibitors; ubiquitin immunoprecipitation of TOP2-DNA complexes; clonogenic survival assays Molecular pharmacology Medium 32587095
2023 Topoisomerase IIα (Top2α) forms abortive Top2-DNA cleavage complexes (Top2ccs) on DNA knots at chromatin bridges during cytokinesis; proteasomal degradation of Top2ccs is required for Rad17 localization to Top2-generated DSB ends; Rad17 then recruits MRN complex and activates ATM-Chk2-INCENP signaling to delay abscission and prevent chromosome breakage, defining the mechanism of the abscission checkpoint. Live-cell imaging; immunofluorescence for Top2α, Top2ccs, Rad17, MRN, ATM-Chk2-INCENP; proteasome inhibitor treatments; Top2α catalytic mutant expression; siRNA knockdowns The Journal of cell biology High 37638884
2023 RAD54L2 promotes TOP2 cleavage complex (TOP2cc) resolution through a novel mechanism: RAD54L2 recognizes sumoylated TOP2 and, using its ATPase activity, promotes TOP2cc resolution and prevents DSB exposure; this mechanism acts together with ZATT/ZNF451 and independently of TDP2. Co-immunoprecipitation; ATPase activity assays; genetic epistasis with TDP2 and ZATT knockouts; TOP2cc resolution assays; DNA damage readouts Science advances Medium 38055822
2022 TOP2A deficiency in trophoblast cells inhibits proliferation, migration, and invasion and activates the FOXO signaling pathway; TOP2A inhibition in mouse pre-implantation embryos impairs trophectoderm differentiation, embryonic mitochondrial function, and developmental rate; TOP2A expression is lower in villi tissues of RSA patients compared to normal pregnancies. shRNA knockdown and overexpression in trophoblast cell lines; in vitro proliferation, migration, invasion assays; FOXO pathway western blotting; mouse embryo culture with TOP2A inhibitor; immunofluorescence; immunohistochemistry on clinical samples Molecular medicine (Cambridge, Mass.) Medium 36585615
2020 Inhibition of TOP2α (using ICRF193 or etoposide) in T cells promotes Top2cc accumulation associated with protein-DNA breaks at genomic DNA, leading to DNA topological disruption and T cell apoptosis; this is linked to diminished TDP2 expression; T cells from patients with chronic viral infection (HBV, HCV, HIV) show lower TOP2α levels and enzymatic activity with Top2cc accumulation. TOP2α enzymatic activity assays; Top2cc measurement in genomic DNA; TDP2 western blotting; apoptosis assays; Top2α inhibitor treatment of primary T cells Cell death & disease Medium 32193368
2022 In zebrafish, TOP2A mutation causes downregulation of autism-associated genes enriched for PRC2 binding sites and H3K27me3; inhibition of the PRC2 component EZH2 rescues social deficits caused by TOP2A inhibition, placing TOP2A upstream of PRC2/H3K27me3 in an evolutionarily conserved pathway governing social behavior development. Drug screen in zebrafish; Top2a mutant zebrafish; RNA-seq; chromatin enrichment for H3K27me3 (H3K27me3 ChIP); EZH2 inhibition rescue; behavioral assays in zebrafish and mice Science advances Medium 36417527
2024 CX-5461 (Pol I transcription inhibitor) induces TOP2α-dependent DNA damage preferentially at ribosomal DNA (rDNA) promoter regions, distinct from canonical TOP2α poisons; sensitivity to CX-5461 in murine Eµ-Myc B lymphoma cells is dependent on cellular TOP2α expression/activity. TOP2α inhibitor and genetic knockdown experiments; RADAR assay for Top2cc detection; γH2AX immunofluorescence at rDNA loci; murine B lymphoma cell line assays; Eµ-Myc model Biomedicines Medium 39062087
2022 TOP2A deficit in decidualizing endometrial stromal cells leads to abnormal decidualization by activating the NF-κB signaling pathway; TOP2A expression is significantly lower in mid-secretory endometrium of women with recurrent implantation failure; TOP2A-deficient mice showed lower fetal weights. shRNA knockdown in T-HESCs; mRNA sequencing; NF-κB pathway western blotting; immunofluorescence; in vivo adenovirus-mediated TOP2A knockdown in mice; clinical sample immunohistochemistry Reproductive biology and endocrinology : RB&E Medium 36138481
2018 TDP2 alone does not remove TOP2-DNA complexes from genomic DNA in vitro; depletion of TDP2 in cells does not slow removal of TOP2-DNA complexes, indicating that prior proteolytic processing steps are required before TDP2 acts on remaining 5'-tyrosine adducts. SUMOylation of TOP2 by ZATT E3 ligase is a proteasome-independent mechanism for TOP2cc processing. TARDIS assay; TDP2 knockdown; in vitro TOP2-DNA complex processing assays; proteasome inhibition; SUMOylated TOP2-DNA complex measurement International journal of molecular sciences Medium 30011940
2022 GINS1 physically interacts with TOP2A; GINS1 promotes TOP2A protein stability through USP15-mediated deubiquitination, thereby driving glioma cell proliferation and migration; USP15 knockdown reduces TOP2A protein levels and mimics TOP2A loss-of-function. Co-immunoprecipitation; USP15 knockdown; TOP2A ubiquitination assays; cell proliferation and invasion assays; in vivo xenograft iScience Medium 36065190
2024 KDM5B demethylase inhibits ZBTB16 transcription by directly reducing H3K4me3 at the ZBTB16 promoter; reduced ZBTB16 subsequently increases TOP2A expression to confer cisplatin resistance; the deubiquitinase USP7 stabilizes KDM5B by deubiquitination, maintaining this KDM5B/ZBTB16/TOP2A axis in NPC. ChIP for H3K4me3 at ZBTB16 promoter; KDM5B inhibition/knockdown; ZBTB16 overexpression rescue experiments; USP7 knockdown and ubiquitination assays; cisplatin sensitivity assays in vitro and in vivo Cell death and differentiation Medium 38287116
2015 Top2 and Sgs1-Top3 act redundantly to ensure replication fork merging and termination at rDNA barriers; absence of both causes checkpoint activation dependent on the fork barrier protein Fob1 and accumulation of asymmetric X-structures at rDNA; either Top2 or Sgs1-Top3 alone is sufficient to prevent a checkpoint-activating structure at the strongest rDNA barrier. Yeast genetics; 2D gel electrophoresis for replication intermediates; checkpoint activation assays; Fob1 epistasis; sgs1, top2, top3 deletion combinations PLoS genetics High 26630413
2023 EZH2 promotes TOP2A expression by H3K27me3-mediated epigenetic silencing of miR-139-5p; TOP2A is a direct target of miR-139-5p (validated by dual-luciferase reporter assay and ChIP for H3K27me3 at the miR-139-5p locus); inhibition of this axis induces cellular senescence and inhibits HCC cell proliferation in vitro and in vivo. Dual-luciferase reporter assay; ChIP for H3K27me3 at miR-139-5p promoter; miRNA inhibitor/mimic experiments; siRNA/shRNA knockdown; SA-β-galactosidase senescence assay; xenograft tumor model Journal of experimental & clinical cancer research : CR Medium 38008711
2022 E2F1 binds directly to the TOP2A promoter and transcriptionally upregulates TOP2A; E2F1 binding sites in the TOP2A promoter region were confirmed by dual-luciferase reporter and ChIP assays; E2F1 silencing decreases TOP2A levels and inhibits GC cell viability and invasion, effects reversed by TOP2A overexpression. ChIP assay; dual-luciferase reporter assay; siRNA knockdown of E2F1; TOP2A overexpression rescue; cell viability and invasion assays Journal of biosciences Medium 36550695
2015 In yeast, TDP1 (tyrosyl-DNA phosphodiesterase 1) participates in repair of Top2α-induced DNA lesions: TDP1-depleted cells accumulate increased amounts of Top2α cleavage complexes after etoposide treatment, show altered kinetics of complex removal, and exhibit increased chromosomal breaks and exchanges; TDP1 acts in NHEJ and alternative end joining but not in homologous recombination for Top2 damage repair. TDP1 shRNA knockdown; Top2α cleavage complex immunodetection in chromatin; γH2AX and pChk1 assays; cytogenetic analysis; micronucleus assay; DNA-PKcs inhibitor epistasis Mutation research Medium 26421495

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2022 Untangling the roles of TOP2A and TOP2B in transcription and cancer. Science advances 176 36322662
2007 Top1- and Top2-mediated topological transitions at replication forks ensure fork progression and stability and prevent DNA damage checkpoint activation. Genes & development 136 17671091
2006 Tyrosyl-DNA phosphodiesterase (Tdp1) participates in the repair of Top2-mediated DNA damage. Proceedings of the National Academy of Sciences of the United States of America 129 16751265
2008 Genomic analysis of the HER2/TOP2A amplicon in breast cancer and breast cancer cell lines. Laboratory investigation; a journal of technical methods and pathology 120 18332872
2017 TOP2A induces malignant character of pancreatic cancer through activating β-catenin signaling pathway. Biochimica et biophysica acta. Molecular basis of disease 111 29045811
2014 Proteolytic degradation of topoisomerase II (Top2) enables the processing of Top2·DNA and Top2·RNA covalent complexes by tyrosyl-DNA-phosphodiesterase 2 (TDP2). The Journal of biological chemistry 101 24808172
2009 Genome-organizing factors Top2 and Hmo1 prevent chromosome fragility at sites of S phase transcription. Cell 98 19737516
2015 TOP2A amplification and overexpression in hepatocellular carcinoma tissues. BioMed research international 92 25695068
2011 Translational control of TOP2A influences doxorubicin efficacy. Molecular and cellular biology 86 21768308
2003 HER-2 and TOP2A coamplification in urinary bladder cancer. International journal of cancer 86 14566826
2017 TOP2A and EZH2 Provide Early Detection of an Aggressive Prostate Cancer Subgroup. Clinical cancer research : an official journal of the American Association for Cancer Research 85 28899973
2019 A nucleotide resolution map of Top2-linked DNA breaks in the yeast and human genome. Nature communications 79 31649282
2021 Transcription-associated topoisomerase 2α (TOP2A) activity is a major effector of cytotoxicity induced by G-quadruplex ligands. eLife 75 34180392
2018 Proliferation and invasion of colon cancer cells are suppressed by knockdown of TOP2A. Journal of cellular biochemistry 75 29761838
2017 TOP2 synergizes with BAF chromatin remodeling for both resolution and formation of facultative heterochromatin. Nature structural & molecular biology 74 28250416
2009 The E3 ubiquitin-ligase Bmi1/Ring1A controls the proteasomal degradation of Top2alpha cleavage complex - a potentially new drug target. PloS one 74 19956605
2013 TOP2A is overexpressed and is a therapeutic target for adrenocortical carcinoma. Endocrine-related cancer 73 23533247
2020 The ZATT-TOP2A-PICH Axis Drives Extensive Replication Fork Reversal to Promote Genome Stability. Molecular cell 67 33296677
2004 Amplification of HER2 and TOP2A and deletion of TOP2A genes in breast cancer investigated by new FISH probes. Acta oncologica (Stockholm, Sweden) 66 15068318
2019 Mutual regulation of MDM4 and TOP2A in cancer cell proliferation. Molecular oncology 55 30672125
2015 Predicting Anthracycline Benefit: TOP2A and CEP17-Not Only but Also. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 54 25897160
1993 The top2-5 mutant of yeast topoisomerase II encodes an enzyme resistant to etoposide and amsacrine. The Journal of biological chemistry 54 8395511
2015 Top2a identifies and provides epigenetic rationale for novel combination therapeutic strategies for aggressive prostate cancer. Oncotarget 53 25605014
1995 A mutation in yeast TOP2 homologous to a quinolone-resistant mutation in bacteria. Mutation of the amino acid homologous to Ser83 of Escherichia coli gyrA alters sensitivity to eukaryotic topoisomerase inhibitors. The Journal of biological chemistry 53 7657608
2023 EZH2-H3K27me3-mediated silencing of mir-139-5p inhibits cellular senescence in hepatocellular carcinoma by activating TOP2A. Journal of experimental & clinical cancer research : CR 51 38008711
2022 TOP2A promotes proliferation and metastasis of hepatocellular carcinoma regulated by miR-144-3p. Journal of Cancer 49 35069905
2011 Condensin phosphorylated by the Aurora-B-like kinase Ark1 is continuously required until telophase in a mode distinct from Top2. Journal of cell science 49 21540296
1996 Human DNA topoisomerases II alpha and II beta can functionally substitute for yeast TOP2 in chromosome segregation and recombination. Molecular & general genetics : MGG 47 8804406
2019 LncRNA SNHG3 promotes clear cell renal cell carcinoma proliferation and migration by upregulating TOP2A. Experimental cell research 45 31505165
2017 Genome-wide TOP2A DNA cleavage is biased toward translocated and highly transcribed loci. Genome research 44 28385713
2016 Physical Proximity of Sister Chromatids Promotes Top2-Dependent Intertwining. Molecular cell 43 27716481
2003 Topoisomerase IIalpha gene (TOP2A) amplification and deletion in cancer--more common than anticipated. Cytopathology : official journal of the British Society for Clinical Cytology 43 14632727
2024 Deubiquitinase USP7 stabilizes KDM5B and promotes tumor progression and cisplatin resistance in nasopharyngeal carcinoma through the ZBTB16/TOP2A axis. Cell death and differentiation 42 38287116
2019 Intercalating TOP2 Poisons Attenuate Topoisomerase Action at Higher Concentrations. Molecular pharmacology 40 31399497
2015 TOP2A gene copy gain predicts response of epithelial ovarian cancers to pegylated liposomal doxorubicin: TOP2A as marker of response to PLD in ovarian cancer. Gynecologic oncology 39 26100858
2015 PTEN stabilizes TOP2A and regulates the DNA decatenation. Scientific reports 39 26657567
2009 Triple negative breast cancer--current status and prospective targeted treatment based on HER1 (EGFR), TOP2A and C-MYC gene assessment. Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia 38 19365520
2023 Targeting long non-coding RNA MALAT1 reverses cancerous phenotypes of breast cancer cells through microRNA-561-3p/TOP2A axis. Scientific reports 34 37244966
2021 Type IIA topoisomerase (TOP2A) triggers epithelial-mesenchymal transition and facilitates HCC progression by regulating Snail expression. Bioengineered 34 34939898
2020 TOP2A Promotes Cell Migration, Invasion and Epithelial-Mesenchymal Transition in Cervical Cancer via Activating the PI3K/AKT Signaling. Cancer management and research 32 32547216
2017 SUMO-Targeted DNA Translocase Rrp2 Protects the Genome from Top2-Induced DNA Damage. Molecular cell 32 28552615
2024 TOP2A modulates signaling via the AKT/mTOR pathway to promote ovarian cancer cell proliferation. Cancer biology & therapy 31 38445610
2020 Inhibition of topoisomerase IIA (Top2α) induces telomeric DNA damage and T cell dysfunction during chronic viral infection. Cell death & disease 30 32193368
2015 Condensin Relocalization from Centromeres to Chromosome Arms Promotes Top2 Recruitment during Anaphase. Cell reports 30 26686624
2011 Expression of p53, Ki-67, E-cadherin, N-cadherin and TOP2A in triple-negative breast cancer. Anticancer research 30 21737670
2022 TOP2A inhibition reverses drug resistance of hepatocellular carcinoma to regorafenib. American journal of cancer research 29 36225636
2020 TOP2A and CENPF are synergistic master regulators activated in cervical cancer. BMC medical genomics 29 33023625
2007 HER-2, TOP2A and chromosome 17 alterations in breast cancer. Pathology oncology research : POR 29 17922046
2022 GINS1 promotes the proliferation and migration of glioma cells through USP15-mediated deubiquitination of TOP2A. iScience 28 36065190
2022 Top2a promotes the development of social behavior via PRC2 and H3K27me3. Science advances 27 36417527
2020 Expression of the Topoisomerase II Alpha (TOP2A) Gene in Lung Adenocarcinoma Cells and the Association with Patient Outcomes. Medical science monitor : international medical journal of experimental and clinical research 27 33361736
2024 Muscone restores anoikis sensitivity in TMZ-resistant glioblastoma cells by suppressing TOP2A via the EGFR/Integrin β1/FAK signaling pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology 23 38723526
2018 Effect of TDP2 on the Level of TOP2-DNA Complexes and SUMOylated TOP2-DNA Complexes. International journal of molecular sciences 23 30011940
2022 Cryptolepine Targets TOP2A and Inhibits Tumor Cell Proliferation in Breast Cancer Cells - An In vitro and In silico Study. Anti-cancer agents in medicinal chemistry 22 35440335
2019 Promoter polymorphisms of TOP2A and ERCC1 genes as predictive factors for chemotherapy in non-small cell lung cancer patients. Cancer medicine 22 31797573
2014 TOP2A gene copy number change in breast cancer. Journal of clinical pathology 22 24403186
2022 TOP2A deficiency leads to human recurrent spontaneous abortion and growth retardation of mouse pre-implantation embryos. Molecular medicine (Cambridge, Mass.) 21 36585615
2020 Ribosomal protein S11 influences glioma response to TOP2 poisons. Oncogene 21 32528131
2024 Expression and potential molecular mechanism of TOP2A in metastasis of non-small cell lung cancer. Scientific reports 20 38806610
2017 TDP2, TOP2, and SUMO: what is ZATT about? Cell research 20 29160298
2024 Low level exposure to BDE-47 facilitates the development of prostate cancer through TOP2A/LDHA/lactylation positive feedback circuit. Environmental research 19 39362459
2023 The role of TOP2A in immunotherapy and vasculogenic mimicry in non-small cell lung cancer and its potential mechanism. Scientific reports 19 37407689
2022 Etoposide-induced DNA damage is increased in p53 mutants: identification of ATR and other genes that influence effects of p53 mutations on Top2-induced cytotoxicity. Oncotarget 19 35178190
2017 ZNF148 modulates TOP2A expression and cell proliferation via ceRNA regulatory mechanism in colorectal cancer. Medicine 19 28072746
2012 Sensitivity to TOP2 targeting chemotherapeutics is regulated by Oct1 and FILIP1L. PloS one 19 22900064
1998 Nuleclear extracts of Crithidia fasciculata contain a factor(s) that binds to the 5'-untranslated regions of TOP2 and RPA1 mRNAs containing sequences required for their cell cycle regulation. The Journal of biological chemistry 19 9726980
2017 Amplification of HER2 and TOP2A and deletion of TOP2A genes in a series of Taiwanese breast cancer. Medicine 18 28079792
2015 Tyrosyl-DNA-phosphodiesterase I (TDP1) participates in the removal and repair of stabilized-Top2α cleavage complexes in human cells. Mutation research 17 26421495
2012 TOP2A RNA expression and recurrence in estrogen receptor-positive breast cancer. Breast cancer research and treatment 17 22706628
1997 Molecular cloning and expression of the Candida albicans TOP2 gene allows study of fungal DNA topoisomerase II inhibitors in yeast. The Biochemical journal 17 9164874
2024 CX-5461 Preferentially Induces Top2α-Dependent DNA Breaks at Ribosomal DNA Loci. Biomedicines 16 39062087
2020 Implications of Topoisomerase (TOP1 and TOP2α) Expression in Patients With Breast Cancer. In vivo (Athens, Greece) 16 33144457
2008 Isolation and characterization of mAMSA-hypersensitive mutants. Cytotoxicity of Top2 covalent complexes containing DNA single strand breaks. The Journal of biological chemistry 16 18723844
2023 Potential Signature Therapeutic Biomarkers TOP2A, MAD2L1, and CDK1 in Colorectal Cancer: A Systems Biomedicine-Based Approach. Biochemical genetics 15 37884851
2022 Knockdown of NUSAP1 inhibits cell proliferation and invasion through downregulation of TOP2A in human glioblastoma. Cell cycle (Georgetown, Tex.) 15 35532155
2022 TOP2A deficit-induced abnormal decidualization leads to recurrent implantation failure via the NF-κB signaling pathway. Reproductive biology and endocrinology : RB&E 15 36138481
2020 The Indenoisoquinoline LMP517: A Novel Antitumor Agent Targeting both TOP1 and TOP2. Molecular cancer therapeutics 14 32430490
2019 Spica Prunellae Extract Enhances Fluorouracil Sensitivity of 5-Fluorouracil-Resistant Human Colon Carcinoma HCT-8/5-FU Cells via TOP2α and miR-494. BioMed research international 14 31662984
2023 Chalcone Derivative CX258 Suppresses Colorectal Cancer via Inhibiting the TOP2A/Wnt/β-Catenin Signaling. Cells 13 37048139
2023 RAD54L2 counters TOP2-DNA adducts to promote genome stability. Science advances 13 38055822
2021 Long Non-Coding RNA (lncRNA) RAMS11 Promotes Metastatis and Cell Growth of Prostate Cancer by CBX4 Complex Binding to Top2α. Cancer management and research 13 33564266
2021 MiR-599 targeting TOP2A inhibits the malignancy of bladder cancer cells. Biochemical and biophysical research communications 13 34284141
2018 The Novel C-terminal Truncated 90-kDa Isoform of Topoisomerase IIα (TOP2α/90) Is a Determinant of Etoposide Resistance in K562 Leukemia Cells via Heterodimerization with the TOP2α/170 Isoform. Molecular pharmacology 13 29514855
2023 CD168+ macrophages promote hepatocellular carcinoma tumor stemness and progression through TOP2A/β-catenin/YAP1 axis. iScience 12 37275516
2023 The abscission checkpoint senses chromatin bridges through Top2α recruitment to DNA knots. The Journal of cell biology 12 37638884
2021 A Role for VCP/p97 in the Processing of Drug-Stabilized TOP2-DNA Covalent Complexes. Molecular pharmacology 12 33941661
2017 Expression and inhibition of BRD4, EZH2 and TOP2A in neurofibromas and malignant peripheral nerve sheath tumors. PloS one 12 28813519
2015 Top2 and Sgs1-Top3 Act Redundantly to Ensure rDNA Replication Termination. PLoS genetics 12 26630413
2003 Light-mediated regulation defines a minimal promoter region of TOP2. Nucleic acids research 12 12954761
2022 Prediction of recurrence from metabolites and expression of TOP2A and EZH2 in prostate cancer patients treated with radiotherapy. NMR in biomedicine 11 35032074
2024 The high expression of TOP2A and MELK induces the occurrence of psoriasis. Aging 10 38382096
2022 E2F1-mediated up-regulation of TOP2A promotes viability, migration, and invasion, and inhibits apoptosis of gastric cancer cells. Journal of biosciences 10 36550695
2020 Small Molecule Inhibitors Confirm Ubiquitin-Dependent Removal of TOP2-DNA Covalent Complexes. Molecular pharmacology 10 32587095
2024 Advances in research on malignant tumors and targeted agents for TOP2A (Review). Molecular medicine reports 9 39670307
2021 Long non‑coding RNA‑DUXAP8 regulates TOP2A in the growth and metastasis of osteosarcoma via microRNA‑635. Molecular medicine reports 9 33982765
2021 Expression Patterns of TOP2A and SIRT1 Are Predictive of Survival in Patients with High-Risk Soft Tissue Sarcomas Treated with a Neoadjuvant Anthracycline-Based Chemotherapy. Cancers 9 34638362
2016 TOP2A copy number and TOP2A expression in uterine benign smooth muscle tumours and leiomyosarcoma. Journal of clinical pathology 9 26994023
2015 Dimerization and thiol sensitivity of the salicylic acid binding thimet oligopeptidases TOP1 and TOP2 define their functions in redox-sensitive cellular pathways. Frontiers in plant science 9 26042129
2024 Knockdown of TOP2A suppresses IL-17 signaling pathway and alleviates the progression of ulcerative colitis. Immunity, inflammation and disease 8 38661103
2022 Evolutionary History of TOPIIA Topoisomerases in Animals. Journal of molecular evolution 8 35165762

Missed literature

Know a paper Affinage missed for TOP2A? Flag it for the maintainers and the community.

No submissions yet.