Affinage

TOP2B

DNA topoisomerase 2-beta · UniProt Q02880

Length
1626 aa
Mass
183.3 kDa
Annotated
2026-06-10
47 papers in source corpus 24 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TOP2B is an ATP-dependent type II DNA topoisomerase that generates transient, controlled double-strand breaks (DSBs) to resolve transcription-associated DNA supercoiling and drive signal-induced transcriptional programs (PMID:20601956, PMID:21228215). It is co-recruited with nuclear receptors and their cofactors to target promoters and enhancers: with androgen receptor at TMPRSS2-ERG breakpoints, where its recombinogenic DSBs generate fusion transcripts (PMID:20601956), and with PARP1 to glucocorticoid receptor target promoters via the BRG1/SWI/SNF complex and Ku70/86, where transient DSBs are required for efficient hormone-stimulated transcription (PMID:26055322). Its catalytic engagement, not mere binding, determines transcriptional output: TOP2B activity at promoters, enhancers, and introns controls expression of oncogenes such as PDGFRA and MYC (PMID:34433651), drives ATRA-induced and long-gene transcriptional programs (PMID:35831557), and underlies activity-dependent early-response gene induction in neurons [PMID:30930055, PMID:bio_10.1101_2025.05.06.652469]. TOP2B catalytic activity is tightly regulated — directly inhibited by PARP1/PARP2 and PAR modification during spermiogenesis (PMID:21228215), suppressed at estrogen-responsive elements through an ERα/ZATT/non-catalytic TOP2A axis that builds negative supercoiling to enable regulatory chromatin contacts (PMID:41296866), and positively favored in gene bodies marked by H3K36me3 (PMID:38377005). TOP2B also shapes 3D genome organization, cooperating with XPF in R-loop processing and with CTCF, cohesin (PDS5A, RAD21), and the nuclear lamina to maintain chromatin looping and LAD/iLAD partitioning (PMID:37939182, PMID:41959374). Under genotoxic stress from TOP2 poisons, ATM and CK1 phosphorylate TOP2B within a degron to trigger SCFβ-TrCP-mediated proteasomal degradation (PMID:32015321), and TOP2B is the principal cellular target of the clinical agent CX-5461 (PMID:34753908). TOP2B is further required for tissue-specific genome integrity and differentiation in ovarian granulosa cells and photoreceptors (PMID:24002654, PMID:28370415).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2002 Medium

    Establishing how TOP2B itself is transcriptionally controlled was needed to understand its constitutive cellular role; the promoter was shown to require NF-Y binding at inverted CCAAT boxes with Sp1 synergy.

    Evidence Deletion/luciferase reporter assays, EMSA, and dominant-negative NF-Y co-transfection

    PMID:12197834

    Open questions at the time
    • Does not address signal-responsive regulation of TOP2B expression
    • No connection to TOP2B catalytic function
  2. 2010 High

    Whether TOP2B-generated DSBs were pathologically consequential was unknown; AR and TOP2B were shown to be co-recruited to TMPRSS2-ERG breakpoints to generate recombinogenic DSBs and fusion transcripts, linking transcription-coupled TOP2B activity to oncogenic rearrangement.

    Evidence ChIP, siRNA knockdown, and RT-PCR fusion-transcript detection in androgen-stimulated cells

    PMID:20601956

    Open questions at the time
    • Mechanism of break repair fidelity not resolved
    • Does not define what controls break frequency
  3. 2011 High

    How TOP2B activity is restrained during chromatin remodeling was unclear; PARP1/PARP2 and PAR modification were shown to directly inhibit TOP2B-mediated breaks during histone-to-protamine exchange, defining a PAR-based regulatory cycle.

    Evidence In vitro TOP2B activity assays with PARP1/2, PARP-knockout mice, and covalent TOP2B-DNA complex measurement in spermatids

    PMID:21228215

    Open questions at the time
    • Whether PAR regulation operates outside spermatogenesis untested here
    • Structural basis of inhibition unknown
  4. 2013 High

    The physiological requirement for TOP2B in proliferating somatic tissue was undefined; granulosa-cell-specific deletion showed TOP2B is needed for DNA integrity, ovulation, and resistance to genotoxic drugs.

    Evidence Cyp19-Cre conditional Top2b knockout mice with DNA damage and ovulation assays

    PMID:24002654

    Open questions at the time
    • Molecular targets in granulosa cells not mapped
    • Transcriptional vs. repair contribution not separated
  5. 2015 High

    How TOP2B is delivered to hormone-responsive promoters was unknown; it was shown to be recruited with PARP1 via the BRG1/SWI/SNF complex through Ku70/86–BRG1 interaction, with its transient DSBs required for GR-stimulated transcription.

    Evidence Co-IP, ChIP, BRG1 domain-mapping pulldowns, and transcription assays with dominant-negative/siRNA

    PMID:26055322

    Open questions at the time
    • Generality across other nuclear receptors not tested
    • How break repair couples to transcription not resolved
  6. 2019 High

    Whether TOP2B DSBs serve as physiological signaling intermediates was open; endogenous TOP2βcc were shown to be required for NGF–AKT–mTORC1 signaling and HSV-1 latency in neurons, and for NMDAR-driven cFos induction in glioblastoma.

    Evidence Pharmacological/genetic TOP2B suppression, TOP2βcc trapping, AKT phosphorylation, viral reactivation, and 53BP1/cFos readouts

    PMID:30841565 PMID:30930055

    Open questions at the time
    • How break number is tuned to signaling output unclear
    • Direct chromatin sites mediating AKT effects not mapped
  7. 2017 Medium

    The role of TOP2B in terminal differentiation was unresolved; retinal conditional knockout showed it cell-autonomously controls photoreceptor transcription-factor and retinopathy gene expression required for outer-segment formation.

    Evidence Conditional KO and mosaic shRNA knockdown with RNA-seq and phenotyping

    PMID:28370415

    Open questions at the time
    • Whether catalytic activity vs. binding drives this not defined
    • Direct vs. indirect target genes not separated
  8. 2020 High

    How cells dispose of poison-trapped TOP2B was unknown; ATM and CK1 were shown to phosphorylate a TOP2B degron enabling SCFβ-TrCP-mediated proteasomal degradation, with degradation blockade impairing repair.

    Evidence Phosphosite mapping, ATM/CK1 inhibition, β-TrCP knockout, Co-IP, ubiquitination, and cell-death assays

    PMID:32015321

    Open questions at the time
    • Whether this pathway acts on non-trapped TOP2B unclear
    • Kinetics relative to repair not defined
  9. 2021 High

    Distinguishing TOP2B occupancy from functional engagement was needed; in gliomas TOP2B regulates PDGFRA and MYC specifically at catalytically active sites correlating with chromatin accessibility, and CX-5461 was reidentified as a TOP2B poison rather than an RNA Pol I inhibitor.

    Evidence ChIP-seq/RNA-seq/ATAC-seq with knockdown and xenografts (#12); in vitro and in vivo TOP2B poisoning panels (#4)

    PMID:34433651 PMID:34753908

    Open questions at the time
    • What restricts catalytic engagement to subsets of bound sites not fully defined
    • Off-target contributions of CX-5461 not fully excluded
  10. 2023 High

    The link between TOP2B and genome architecture was undefined; XPF was shown to recruit TOP2B to active promoters for R-loop processing, and TOP2B loss diminishes XPF, CTCF, and cohesin recruitment and impairs CTCF-mediated looping.

    Evidence Co-IP, ChIP-seq (TOP2B/XPF/CTCF/SMC1A/SMC3), R-loop assays, and chromosome conformation capture

    PMID:37939182

    Open questions at the time
    • Order of recruitment among partners not fully resolved
    • Whether catalytic activity is required for looping not separated from binding
  11. 2024 High

    What controls genome-wide TOP2B catalytic engagement and its transcriptional consequences was unknown; mapping of TOP2βcc showed H3K36me3 promotes engagement in gene bodies while high Pol II reduces promoter TOP2βcc, and that an ERα/ZATT/TOP2A axis inhibits TOP2B to build negative supercoiling enabling estrogen-responsive contacts.

    Evidence Genome-wide TOP2βcc mapping with histone-mark ChIP-seq and nascent transcription (#8); ChIP-seq, supercoiling assays, ZATT/TOP2A/ERα perturbation, and 3C (#9)

    PMID:38377005 PMID:41296866

    Open questions at the time
    • How chromatin marks mechanistically license cleavage unclear
    • Whether supercoiling-driven contacts generalize beyond estrogen response untested
  12. 2024 Medium

    How TOP2B integrates with higher-order nuclear organization and disease regulation was addressed: TOP2B binds inter-LAD chromatin and partners with LBR for lamina partitioning, and a GCN5–DNA-PKcs axis transcriptionally represses TOP2B in anthracycline-resistant AML.

    Evidence DamID/Hi-C with TOP2B and LBR depletion (#18, preprint); ChIP of DNA-PKcs at TOP2B promoter with genetic perturbation in primary AML and xenografts (#13)

    PMID:38240344 PMID:bio_10.1101_2024.10.01.616012

    Open questions at the time
    • LAD-partitioning role rests on a single preprint
    • Whether DNA-PKcs repression is direct vs. structural not fully resolved
  13. 2025 Medium

    Multiple specialized roles were defined: TOP2B cooperates with ATRX to resolve G-quadruplexes during replication, with PDS5A/CTCF for loop formation, in transcriptional memory via repeated DSB cycles at neuronal ERGs, and relocalizes to cytoplasmic vaccinia factories via A50, while UTX and the metabolite PNU142586 act as regulators/inhibitors.

    Evidence Co-IP, ChIP-seq, DNA-fiber and Hi-C assays (#15, #22), 3C/4C with targeted DSBs (#17), domain-mapping and virology (#16), conditional KO with rescue (#20), and in vitro enzymatic assays (#23)

    PMID:40435237 PMID:40990248 PMID:41385502 PMID:41959374 PMID:bio_10.1101_2025.02.05.636656 PMID:bio_10.1101_2025.05.06.652469

    Open questions at the time
    • Several mechanisms rest on single-lab or preprint evidence
    • Cytoplasmic and transcriptional-memory functions await reconstitution and independent confirmation

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how chromatin context, partner availability, and DSB repair kinetics are jointly decoded to determine where TOP2B catalytic engagement produces productive transcription versus pathological breaks.
  • No unified model linking cleavage-complex resolution to transcriptional outcome
  • Structural basis for site-selective catalytic licensing undefined
  • Causal hierarchy among TOP2B, CTCF, cohesin, and lamina partners not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140097 catalytic activity, acting on DNA 5 GO:0140110 transcription regulator activity 3 GO:0003677 DNA binding 2 GO:0140657 ATP-dependent activity 1
Localization
GO:0005634 nucleus 3 GO:0000228 nuclear chromosome 2 GO:0005635 nuclear envelope 1
Pathway
R-HSA-4839726 Chromatin organization 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-73894 DNA Repair 3 R-HSA-1266738 Developmental Biology 2 R-HSA-162582 Signal Transduction 2
Partners
ATRXBRG1CTCFPARP1PDS5ATOP2AXPFZATT
Complex memberships
BRG1/SWI/SNF complex

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 Androgen receptor and TOP2B are co-recruited to TMPRSS2-ERG genomic breakpoints upon androgen stimulation, triggering recombinogenic TOP2B-mediated DNA double-strand breaks (DSBs) that generate TMPRSS2-ERG fusion transcripts; this process requires both TOP2B and components of the DSB repair machinery. Chromatin immunoprecipitation (ChIP), siRNA knockdown, RT-PCR detection of fusion transcripts in androgen-stimulated cells Nature genetics High 20601956
2015 TOP2B (topoisomerase IIβ), together with PARP1, is recruited to nuclear receptor target gene promoters through the BRG1/SWI/SNF complex via a direct interaction between Ku70/86 and the HSA/BRK domains of BRG1; transient TOP2B-mediated DSBs at these promoters are required for efficient glucocorticoid receptor (GR)-stimulated transcription. Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), transcriptional activation assays with dominant-negative constructs and siRNA knockdown, BRG1 domain-mapping pulldown Molecular and cellular biology High 26055322
2011 PARP1 and PARP2 directly inhibit TOP2B activity in vitro; poly(ADP-ribose) (PAR) modification suppresses TOP2B-mediated DNA strand breaks in elongating spermatids, and this inhibition is reversed by PAR glycohydrolase, establishing a regulatory cycle that coordinates TOP2B-dependent DNA relaxation with histone-to-protamine exchange during spermiogenesis. In vitro TOP2B activity assay with PARP1/PARP2; pharmacological and genetic PARP inhibition in vivo; measurement of covalent TOP2B-DNA complexes in murine spermatids Biology of reproduction High 21228215
2020 In response to TOP2 poison (teniposide/VM-26), ATM kinase and CK1 cooperatively phosphorylate TOP2B on Ser1134 and Ser1130 within a canonical degron motif, enabling β-TrCP binding and SCFβ-TrCP-mediated ubiquitin-proteasomal degradation of TOP2B; blocking this degradation impairs DNA damage repair and accelerates apoptosis. Phosphorylation site mapping, pharmacological inhibition of ATM and CK1, genetic knockdown/knockout of β-TrCP and ATM, Co-IP of TOP2B with β-TrCP, ubiquitination assays, cell death assays Oncogenesis High 32015321
2021 CX-5461, previously classified as an RNA Pol I inhibitor, acts primarily as a TOP2B poison at pharmacologically relevant concentrations; comprehensive in vitro and in vivo assays demonstrated its primary target is TOP2B rather than RNA Pol I, with implications for therapy-induced leukemia and cardiotoxicity. Comprehensive panel of in vitro TOP2B/TOP2A poisoning assays, cellular DNA damage assays, in vivo orthotopic patient-derived xenograft neuroblastoma models Nature communications High 34753908
2013 TOP2B is required for DNA integrity in granulosa cells (GCs) of growing ovarian follicles; GC-specific deletion of Top2b using Cyp19-Cre in mice causes DNA damage accumulation, follicle atresia, decreased ovulation, and hypersensitivity to genotoxic chemotherapeutic drugs. Conditional knockout mouse model (Cyp19-Cre × Top2b flox), DNA damage checkpoint assays, ovulation assays, gonadotropin stimulation Molecular endocrinology High 24002654
2019 Endogenous TOP2B-mediated DNA double-strand breaks (TOP2βcc intermediates) in neurons are required for NGF-dependent AKT-mTORC1 signaling and maintenance of HSV-1 latency; suppression of DNA repair pathways that remove TOP2βcc triggers HSV-1 reactivation, linking TOP2B catalytic activity to AKT signaling dynamics. Pharmacological inhibition and genetic suppression of TOP2B in primary neurons; TOP2βcc trapping assays; AKT phosphorylation assays; viral reactivation assays; PHLPP1 knockdown Molecular cell High 30930055
2023 XPF physically interacts with TOP2B and recruits it to active gene promoters; TOP2B is required for XPF-dependent R-loop processing, leading to DSB accumulation and DNA damage response activation at active promoters. Abrogation of TOP2B diminishes recruitment of XPF, CTCF, and cohesin subunits to promoters and impairs CTCF-mediated DNA looping. Co-immunoprecipitation of XPF with TOP2B, ChIP-seq for TOP2B/XPF/CTCF/SMC1A/SMC3, siRNA knockdown of TOP2B, R-loop detection assays, chromosome conformation capture Science advances High 37939182
2024 Genome-wide mapping of catalytically engaged TOP2B (trapped as covalent cleavage complexes) in cortical neurons shows that TOP2Bcc distribution is influenced by nucleosome organization and compartmental chromosome architecture; H3K36me3 positively regulates TOP2B catalytic engagement in gene bodies, while high RNA Pol II occupancy at active promoters correlates with reduced TOP2Bccs; poisoning or inhibiting TOP2B increases nascent transcription at most genes but reduces transcription within long genes via effects on intragenic enhancers. Genome-wide trapping and mapping of TOP2Bccs (ICE-seq/analogous method), ChIP-seq for TOP2B and histone marks, nascent transcription assays, pharmacological inhibition/poisoning Cell reports High 38377005
2024 Estrogen-mediated inhibition of TOP2B catalytic activity (but not binding) at estrogen-responsive enhancers and promoters depends on estrogen receptor α (ERα), a non-catalytic function of TOP2A, and the SUMO-ligase ZATT; this inhibition causes accumulation of negative DNA supercoiling and promotes formation of regulatory chromatin contacts required for the estrogen transcriptional response. ChIP-seq for TOP2B binding and activity, supercoiling assays, ZATT/TOP2A knockdown/knockout, ERα manipulation, chromosome conformation capture, TOP2B catalytic activity measurements in cells Science advances High 41296866
2019 NMDA receptor activation induces TOP2B-dependent DNA double-strand breaks in glioblastoma cells, and TOP2B activity is required downstream of NMDAR signaling for expression of the proto-oncogene cFos; siRNA knockdown of TOP2B reduced cFos expression and increased radiosensitivity. siRNA knockdown of TOP2B, immunofluorescence for DSB markers (53BP1), Western blot for cFos, pharmacological inhibition of NMDAR/CREB/TOP2B, clonogenic survival assay Cancers Medium 30841565
2017 TOP2B cell-autonomously controls the expression of key photoreceptor transcription factors and retinopathy-related genes (e.g., Crx, Nr2e3, Opn1sw, Abca4, Bbs7, Pde6b) during late-stage photoreceptor differentiation, and its loss causes defective outer segment formation without immediate dramatic cell loss. Top2b conditional knockout in retina, shRNA-mediated mosaic knockdown via in vivo electroporation, RNA-seq analysis, phenotypic characterization of outer segments and synapses Journal of neuroscience research Medium 28370415
2021 TOP2B regulates transcription of multiple oncogenes in gliomas (including PDGFRA and MYC) specifically at genomic sites where it is catalytically active (in promoters, enhancers, and introns), not merely at all binding sites; TOP2B activity correlates with chromatin accessibility at these sites. ChIP-seq for TOP2B, RNA-seq, ATAC-seq, gene silencing, mouse xenograft in vivo experiments Clinical cancer research Medium 34433651
2024 DNA-PKcs directly binds the TOP2B promoter upstream region and acts as a transcriptional repressor of TOP2B expression in anthracycline-resistant AML cells; GCN5 (KAT2A) mediates transcriptional upregulation of DNA-PKcs in AML relapse, establishing a GCN5-DNA-PKcs-TOP2B transcriptional regulatory axis underlying anthracycline resistance. ChIP of DNA-PKcs at TOP2B promoter, genetic knockdown/overexpression of DNA-PKcs and GCN5, patient-derived primary AML cultures, xenograft mouse model Journal of cell science Medium 38240344
2022 TOP2B is required for ATRA-induced transcriptional activation of many rapidly induced genes in SH-SY5Y neuroblastoma cells (including BCL2, CYP26A1, CRABP2, NTRK2); long genes and highly expressed genes are disproportionately dependent on TOP2B; loss of TOP2B causes upregulation of mesenchymal markers and NOTCH signaling, shifting cells from adrenergic to mesenchymal transcriptional state. Pharmacological inhibition of TOP2B and targeted CRISPR gene inactivation (TOP2B null cells), RNA-seq comparison of WT vs. TOP2B null cells with and without ATRA treatment Molecular neurobiology Medium 35831557
2025 TOP2B cooperates with ATRX to resolve G-quadruplex (G4) structures during DNA replication; CX-5461 acts as a TOP2B poison that selectively impairs TOP2B binding at G4 sites, leading to G4 accumulation, replication fork stalling, and MRE11-dependent degradation of stalled forks, with enhanced effects in ATRX-deficient glioma cells. G4 immunofluorescence, replication fork assays (DNA fiber), Co-IP of ATRX-TOP2B, CX-5461 treatment with TOP2B ChIP-seq, genetic ATRX/TOP2B manipulation Nucleic acids research Medium 40990248
2025 During vaccinia virus infection, early viral protein synthesis induces cytoplasmic relocalization of TOP2B; TOP2B is recruited to cytoplasmic viral factories through interaction of its C-terminal domain with the viral ligase A50; in the cytoplasm, TOP2B suppresses viral replication by enhancing formation of double-stranded RNA and antiviral granules containing tRNA splicing ligase components. Protein interaction studies (C-terminal domain mapping), live cell imaging of TOP2B relocalization, virology assays with TOP2B knockdown/knockout, dsRNA detection bioRxivpreprint Medium bio_10.1101_2025.02.05.636656
2025 TOP2B-mediated DSBs within promoters of early response genes (Fos, Npas4) in neurons are sufficient to recapitulate enhancer-promoter contact profiles observed after neuronal stimulation; repeated DSB cycles progressively potentiate ERG induction (transcriptional memory effect) and are associated with loss of cis chromosome interactions and gain of trans interactions at ERG promoters. 3C and 4C-seq chromosome conformation capture, targeted DSB induction, nascent transcription assays, repeated stimulation paradigms in mouse cortical neurons and HEK293T cells bioRxivpreprint Medium bio_10.1101_2025.05.06.652469
2024 TOP2B binds predominantly to inter-LAD (iLAD) chromatin and its depletion results in partial loss of genome partitioning between LADs and iLADs; TOP2B depletion preferentially disrupts genome interactions with lamin B receptor (LBR) over lamins; co-depletion of TOP2B and LBR causes partial LAD/iLAD inversion resembling oncogene-induced senescence, supporting a coordinated TOP2B(iLAD)/LBR(LAD) axis for nuclear lamina organization. DamID and Hi-C for LAD mapping, TOP2B ChIP-seq, siRNA depletion of TOP2B and LBR, genome-nuclear lamina interaction assays bioRxivpreprint Medium bio_10.1101_2024.10.01.616012
2002 TOP2B promoter activity is constant throughout the cell cycle and requires direct binding of NF-Y transcription factor to two inverted CCAAT boxes (ICBs) in the region -533 to -481 upstream; an Sp1-binding GC box just upstream of the ICBs synergistically contributes to promoter activity; dominant-negative NF-Y subunit A ablates promoter activity. 5'-serial and internal deletion luciferase reporter assays, gel mobility-shift assays (EMSA), dominant-negative co-transfection, mutational analysis of regulatory elements The Biochemical journal Medium 12197834
2025 UTX (KDM6A) directly binds the TOP2β (Top2b) promoter and acts as a transcriptional repressor; UTX deletion in spinal cord microvascular endothelial cells upregulates Top2β, reduces cellular senescence, and promotes proliferation/angiogenesis after spinal cord injury; knockdown of Top2β reverses the anti-senescence effects of UTX deletion. ChIP-seq and ChIP-qPCR for UTX at Top2b promoter, endothelial-specific UTX knockout mice (UTXflox/flox × Tek-Cre), RNA-seq, Top2b knockdown rescue experiment, senescence assays PloS one Medium 41385502
2015 TOP2B occupancy across the human genome (ChIP-seq in MCF7 cells) shows enrichment at gene promoters and within 5 kb of transcription start sites; TOP2B peaks coincide with binding motifs for SP1, KLF4, TFAP2A, CTCF, ESR1/ESR2, and REST; genes associated with TOP2B peaks are enriched for neuronal development and axon guidance ontology terms. Whole-genome ChIP-seq with three different peak-calling methods, transcription factor motif analysis, Gene Ontology analysis Biology open Medium 26459242
2025 PDS5A (a regulatory cohesin subunit) and TOP2B cooperate for their mutual recruitment to CTCF-bound chromatin; catalytically active TOP2B increases PDS5A occupancy genome-wide; a novel PDS5A-CTCF interaction region (CTCF N-terminal residues 95-116) is required for CTCF-PDS5A-TOP2B interaction in vitro and for TOP2B-mediated enrichment of PDS5A in vivo; loss of this interaction reduces chromatin loop number. Co-IP (CTCF-PDS5A-TOP2B), ChIP-seq for PDS5A and TOP2B, in vitro interaction mapping with CTCF truncations, inducible PDS5A knockdown, Hi-C chromatin loop analysis bioRxivpreprint Medium 41959374
2025 PNU142586, a primary metabolite of linezolid, targets TOP2B (and TOP2A) by impeding DNA binding to TOP2B in a conformation favorable for cleavage and by inhibiting ATP hydrolysis; these biochemical effects cause disruption of transcription and antiproliferative/cytotoxic outcomes including mitochondrial dysfunction. Molecular docking, in vitro TOP2B enzymatic assays (DNA binding, ATP hydrolysis), cellular DNA damage assays, in vivo experiments Science advances Medium 40435237

Source papers

Stage 0 corpus · 47 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Androgen-induced TOP2B-mediated double-strand breaks and prostate cancer gene rearrangements. Nature genetics 502 20601956
2022 Untangling the roles of TOP2A and TOP2B in transcription and cancer. Science advances 176 36322662
2018 TOP2B: The First Thirty Years. International journal of molecular sciences 90 30223465
2021 The chemotherapeutic CX-5461 primarily targets TOP2B and exhibits selective activity in high-risk neuroblastoma. Nature communications 75 34753908
2015 Glucocorticoid Receptor Transcriptional Activation via the BRG1-Dependent Recruitment of TOP2β and Ku70/86. Molecular and cellular biology 70 26055322
1998 Structural organization of the human TOP2A and TOP2B genes. Gene 60 9795238
2011 Poly(ADP-ribose) polymerases PARP1 and PARP2 modulate topoisomerase II beta (TOP2B) function during chromatin condensation in mouse spermiogenesis. Biology of reproduction 59 21228215
2015 Genome-wide ChIP-seq analysis of human TOP2B occupancy in MCF7 breast cancer epithelial cells. Biology open 43 26459242
2019 TOP2β-Dependent Nuclear DNA Damage Shapes Extracellular Growth Factor Responses via Dynamic AKT Phosphorylation to Control Virus Latency. Molecular cell 34 30930055
2020 Berberine chloride suppresses non-small cell lung cancer by deregulating Sin3A/TOP2B pathway in vitro and in vivo. Cancer chemotherapy and pharmacology 32 32607786
2005 NUP98 is fused to topoisomerase (DNA) IIbeta 180 kDa (TOP2B) in a patient with acute myeloid leukemia with a new t(3;11)(p24;p15). Clinical cancer research : an official journal of the American Association for Cancer Research 27 16166424
2021 TOP2B's contributions to transcription. Biochemical Society transactions 25 34747992
2002 Characterization of the human topoisomerase IIbeta (TOP2B) promoter activity: essential roles of the nuclear factor-Y (NF-Y)- and specificity protein-1 (Sp1)-binding sites. The Biochemical journal 25 12197834
2022 TOP2B Is Required to Maintain the Adrenergic Neural Phenotype and for ATRA-Induced Differentiation of SH-SY5Y Neuroblastoma Cells. Molecular neurobiology 24 35831557
2017 Global developmental delay and intellectual disability associated with a de novo TOP2B mutation. Clinica chimica acta; international journal of clinical chemistry 24 28343847
2013 TOP2β is essential for ovarian follicles that are hypersensitive to chemotherapeutic drugs. Molecular endocrinology (Baltimore, Md.) 19 24002654
2020 SCFβ-TrCP-mediated degradation of TOP2β promotes cancer cell survival in response to chemotherapeutic drugs targeting topoisomerase II. Oncogenesis 18 32015321
2019 Mutations in TOP2B cause autosomal-dominant hereditary hearing loss via inhibition of the PI3K-Akt signalling pathway. FEBS letters 17 31198993
2017 Top2b is involved in the formation of outer segment and synapse during late-stage photoreceptor differentiation by controlling key genes of photoreceptor transcriptional regulatory network. Journal of neuroscience research 15 28370415
2023 To Break or Not to Break: The Role of TOP2B in Transcription. International journal of molecular sciences 14 37834253
2019 NMDA Receptor Signaling Mediates cFos Expression via Top2β-Induced DSBs in Glioblastoma Cells. Cancers 14 30841565
2012 Do transcription factories and TOP2B provide a recipe for chromosome translocations in therapy-related leukemia? Cell cycle (Georgetown, Tex.) 14 22894901
2022 All-trans retinoic acid (ATRA) regulates key genes in the RARG-TOP2B pathway and reduces anthracycline-induced cardiotoxicity. PloS one 12 36331922
2012 High TOP2B/TOP2A expression ratio at diagnosis correlates with favourable outcome for standard chemotherapy in acute myeloid leukaemia. British journal of cancer 12 22627319
2020 A de novo TOP2B variant associated with global developmental delay and autism spectrum disorder. Molecular genetics & genomic medicine 11 31953910
2023 XPF interacts with TOP2B for R-loop processing and DNA looping on actively transcribed genes. Science advances 9 37939182
2024 Mapping catalytically engaged TOP2B in neurons reveals the principles of topoisomerase action within the genome. Cell reports 7 38377005
2021 TOP2B Enzymatic Activity on Promoters and Introns Modulates Multiple Oncogenes in Human Gliomas. Clinical cancer research : an official journal of the American Association for Cancer Research 6 34433651
2025 Deciphering linezolid-induced hematologic toxicity: Targeting TOP2A and TOP2B via its primary metabolite PNU142586. Science advances 4 40435237
2024 DNA-PKcs-mediated transcriptional regulation of TOP2B drives chemoresistance in acute myeloid leukemia. Journal of cell science 4 38240344
2020 Copy number variations of TOP2B gene are associated with growth traits in Chinese sheep breeds. Animal biotechnology 4 32498592
1995 [Cloning and analysis of the nucleotide sequence of the segment in the Mycoplasma gallisepticum genome containing the gene for the ATP-binding subunit of DNA topoisomerase type II (topIIB)]. Molekuliarnaia biologiia 4 7783737
2024 Targeting TOP2B as a vulnerability in aging and aging-related diseases. Biochimica et biophysica acta. Molecular basis of disease 3 38296114
2025 Identification of a novel TOP2B::AFF2 fusion gene in B-cell acute lymphoblastic leukemia. Scientific reports 2 39863655
2025 SiRNA-mediated knockdown of TOP2B protects hiPSC-derived cardiomyocytes from doxorubicin-induced toxicity. Life sciences 2 40158615
2024 Topological regulation of the estrogen transcriptional response by ZATT-mediated inhibition of TOP2B activity. bioRxiv : the preprint server for biology 2 38328138
2023 Revisiting TOP2B-related phenotypes: Three new cases and literature review. Clinical genetics 2 37068767
2025 Top2b-Regulated Genes and Pathways Linked to Retinal Homeostasis and Degeneration. Cells 1 40558514
2025 Infantile epileptic spasms syndrome as a new phenotype in TOP2B deficiency caused by a de novo variant: a case report and literature review. Frontiers in pediatrics 1 40656194
2025 TOP2B modulates DNA supercoiling and chromatin contacts during transcriptional induction. Science advances 1 41296866
2026 PDS5A and TOP2B cooperate for chromatin recruitment via CTCF. bioRxiv : the preprint server for biology 0 41959374
2026 Integrated Global Phosphoproteomic, Bioinformatic, and Machine Learning Analysis Reveals Regulatory Networks of TOP1, TOP2A, TOP2B, and C1orf35 in Hepatocellular Carcinoma (HCC). Oncology research 0 42065042
2026 Deletion of TOP2B promoter using CRISPR-Cas9 induces senescence in HEK 293T cells. Biochemistry and biophysics reports 0 42211003
2025 TOP2B is required for compartment strength changes upon retinoic acid treatment in SH-SY5Y cells. Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology 0 40183884
2025 Top2b regulates morphological and migratory properties of retinal progenitor cells in vivo and upon transplantable matrix substrates. Exploration of biomat-x 0 40893167
2025 ATRX cooperates with TOP2B for replication fork stability and DNA damage response through G-quadruplex regulation. Nucleic acids research 0 40990248
2025 UTX/Top2β axis mediated spinal cord microvascular endothelial cells senescence exacerbates spinal cord injury. PloS one 0 41385502

Missed literature

Know a paper Affinage missed for TOP2B? Flag it for the maintainers and the community.

No submissions yet.