DNA topoisomerase 2-alpha is an essential nuclear enzyme that controls DNA topology by catalyzing ATP-dependent double-strand passage reactions. It resolves DNA supercoiling, unknots DNA, and decatenates interlinked sister chromatids. TOP2A is absolutely required for DNA replication, chromosome condensation, and mitotic chromosome segregation in proliferating cells.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003918 DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity | IBA GO_REF:0000033 | ACCEPT | Summary: This is the core molecular function of TOP2A. The enzyme catalyzes ATP-dependent double-strand DNA passage to resolve topological entanglements. Reason: This correctly captures TOP2A's primary catalytic function as confirmed by biochemical assays (PMID:15491148, PMID:12711669, PMID:16611985, PMID:22323612). Supporting Evidence: file:human/TOP2A/TOP2A-deep-research-openai.md TOP2A encodes a critical enzyme that controls DNA topology. It can cut and rejoin double-stranded DNA to resolve DNA tangles and supercoils. This enzyme works as a homodimer and uses ATP hydrolysis to drive a strand-passage reaction file:human/TOP2A/TOP2A-deep-research-falcon.md TOP2A catalyzes an **ATP-dependent duplex DNA strand-passage reaction**. Mechanistically, it binds a βgateβ DNA segment (G-segment), cleaves both strands, transports a second duplex (T-segment) through the break, and then reseals the G-segment. file:human/TOP2A/TOP2A-deep-research-falcon.md A catalytic **tyrosine** performs a nucleophilic attack on the DNA phosphodiester backbone to form a **covalent 5β²-phosphotyrosyl TOP2AβDNA intermediate** (a reversible cleavage complex) that protects the DNA ends during the cycle. PMID:15491148 DNA ligation catalyzed by human topoisomerase II alpha. PMID:12711669 RNA helicase A interacts with dsDNA and topoisomerase IIalpha. PMID:16611985 Protein kinase C delta activates topoisomerase IIalpha to induce apoptotic cell death in response to DNA damage. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: TOP2A is predominantly nuclear. Reason: Well-established localization supported by multiple IDA studies (PMID:9155056, PMID:10959840, PMID:10788521, PMID:16611985). The deep research states 'Topo IIΞ± is predominantly a nuclear enzyme. It localizes to the cell nucleus, where the chromosomal DNA is housed'. Contains multiple nuclear localization sequences. Supporting Evidence: file:human/TOP2A/TOP2A-deep-research-openai.md Topo IIΞ± is predominantly a nuclear enzyme. It localizes to the cell nucleus, where the chromosomal DNA is housed. The protein contains multiple Nuclear Localization Sequences (NLS) in its C-terminal domain that ensure its import into the nucleus file:human/TOP2A/TOP2A-deep-research-falcon.md TOP2A is **nuclear** and becomes strongly associated with mitotic chromosomes, including enrichment along chromosome axes/scaffold, consistent with a direct role in **mitotic chromosome condensation, individualization, and segregation**. ... A mitochondrial role for TOP2 isoforms is not supported in the retrieved evidence: a systematic analysis of human topoisomerase localization/activity found **no evidence for TOP2 localization to mitochondria**. PMID:9155056 The distribution and expression of the two isoforms of DNA topoisomerase II in normal and neoplastic human tissues. PMID:10959840 DNA topoisomerase IIalpha interacts with CAD nuclease and is involved in chromatin condensation during apoptotic execution. PMID:10788521 Modulation of human DNA topoisomerase IIalpha function by interaction with 14-3-3epsilon. PMID:16611985 Protein kinase C delta activates topoisomerase IIalpha to induce apoptotic cell death in response to DNA damage. |
| GO:0000819 sister chromatid segregation | IBA GO_REF:0000033 | ACCEPT | Summary: More specific than chromosome segregation - TOP2A decatenates sister chromatids. Reason: This IBA annotation is more specific than GO:0007059 and correctly emphasizes the sister chromatid decatenation function. This is a core role of TOP2A in mitosis. Falcon deep research confirms TOP2A is the major mitotic chromosome-associated type II isoform required for decatenation of intertwined sister DNAs. Supporting Evidence: file:human/TOP2A/TOP2A-deep-research-openai.md It can also untangle interlinked sister chromatids after DNA replication β a process known as decatenation. TOP2A is required to alleviate topological stress. By resolving torsional strain and decatenating replicated DNA, TOP2A enables replication to complete and prepares chromosomes for segregation file:human/TOP2A/TOP2A-deep-research-falcon.md DNA catenanes** (interlinked sister chromatids) requiring **decatenation** during mitosis. file:human/TOP2A/TOP2A-deep-research-falcon.md In mitosis, TOP2A is emphasized as the major chromosome-associated isoform required for proper chromosome individualization/segregation, while TOP2B is less tightly chromatin-associated in mitosis in the same discussions. |
| GO:0000712 resolution of meiotic recombination intermediates | IBA GO_REF:0000033 | ACCEPT | Summary: TOP2A resolves DNA entanglements during meiotic recombination. Reason: IBA annotation suggesting TOP2A orthologs function in resolving meiotic recombination intermediates. While TOP2A is highly expressed in proliferating cells, it is also expressed in germline cells and could resolve topologically complex DNA structures arising from recombination. |
| GO:0030263 apoptotic chromosome condensation | IBA GO_REF:0000033 | ACCEPT | Summary: TOP2A is involved in chromosome condensation during apoptosis. Reason: Demonstrated in PMID:10959840, which showed 'DNA topoisomerase IIΞ± interacts with CAD nuclease and is involved in chromatin condensation during apoptotic execution'. This is a specific role in apoptosis. Supporting Evidence: PMID:10959840 DNA topoisomerase IIΞ± interacts with CAD nuclease and is involved in chromatin condensation during apoptotic execution |
| GO:0000166 nucleotide binding | IEA GO_REF:0000043 | ACCEPT | Summary: TOP2A binds nucleotides (ATP). Reason: This is a very general parent term of ATP binding. Correct but uninformative compared to more specific terms. |
| GO:0003677 DNA binding | IEA GO_REF:0000120 | ACCEPT | Summary: TOP2A binds DNA as part of its mechanism, but this is too general for the core function. Reason: TOP2A does bind DNA directly as confirmed by biochemical studies (PMID:12079377, PMID:10788521, PMID:9049244, PMID:22323612). However, this is a very general molecular function term. The enzyme's DNA binding is integral to its topoisomerase activity, and this annotation provides useful but non-specific information about the protein's molecular capabilities. Supporting Evidence: PMID:22323612 DNA cleavage and opening reactions of human topoisomerase IIΞ± are regulated via Mg2+-mediated dynamic bending of gate-DNA PMID:12079377 The ATP-operated clamp of human DNA topoisomerase IIalpha: hyperstimulation of ATPase by "piggy-back" binding. PMID:10788521 Modulation of human DNA topoisomerase IIalpha function by interaction with 14-3-3epsilon. PMID:9049244 Cell cycle-coupled relocation of types I and II topoisomerases and modulation of catalytic enzyme activities. |
| GO:0003682 chromatin binding | IEA GO_REF:0000117 | ACCEPT | Summary: TOP2A binds chromatin, especially during mitosis when it is a major chromosome scaffold component. Reason: Well-supported by experimental evidence (PMID:9049244). The deep research emphasizes that 'Topo IIΞ± is a major component of the mitotic chromosome scaffold' and 'proteomic analyses of isolated human chromosomes identified Topo IIΞ± as a major scaffold protein'. This binding is functionally important for chromosome structure. Supporting Evidence: file:human/TOP2A/TOP2A-deep-research-openai.md Topo IIΞ± is a major component of the mitotic chromosome scaffold. Proteomic analyses of isolated human chromosomes identified Topo IIΞ± as a major scaffold protein that remains bound after high-salt extractions, consistent with an architectural role file:human/TOP2A/TOP2A-deep-research-falcon.md TOP2A is **nuclear** and becomes strongly associated with mitotic chromosomes, including enrichment along chromosome axes/scaffold, consistent with a direct role in **mitotic chromosome condensation, individualization, and segregation**. PMID:9049244 Cell cycle-coupled relocation of types I and II topoisomerases and modulation of catalytic enzyme activities. |
| GO:0003916 DNA topoisomerase activity | IEA GO_REF:0000043 | ACCEPT | Summary: This is a parent term of GO:0003918. Less specific than the type II annotation. Reason: While correct, this is broader than GO:0003918 (DNA topoisomerase type II activity). Both annotations can coexist - the more specific IBA/IDA annotations capture the type II specificity, while this IEA annotation provides a general classification. |
| GO:0003918 DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity | IEA GO_REF:0000120 | ACCEPT | Summary: This is the core molecular function of TOP2A. The enzyme catalyzes ATP-dependent double-strand DNA passage to resolve topological entanglements. Reason: This correctly captures TOP2A's primary catalytic function as confirmed by biochemical assays (PMID:15491148, PMID:12711669, PMID:16611985, PMID:22323612). Supporting Evidence: file:human/TOP2A/TOP2A-deep-research-openai.md TOP2A encodes a critical enzyme that controls DNA topology. It can cut and rejoin double-stranded DNA to resolve DNA tangles and supercoils. This enzyme works as a homodimer and uses ATP hydrolysis to drive a strand-passage reaction file:human/TOP2A/TOP2A-deep-research-falcon.md TOP2A catalyzes an **ATP-dependent duplex DNA strand-passage reaction**. Mechanistically, it binds a βgateβ DNA segment (G-segment), cleaves both strands, transports a second duplex (T-segment) through the break, and then reseals the G-segment. file:human/TOP2A/TOP2A-deep-research-falcon.md A catalytic **tyrosine** performs a nucleophilic attack on the DNA phosphodiester backbone to form a **covalent 5β²-phosphotyrosyl TOP2AβDNA intermediate** (a reversible cleavage complex) that protects the DNA ends during the cycle. PMID:15491148 DNA ligation catalyzed by human topoisomerase II alpha. PMID:12711669 RNA helicase A interacts with dsDNA and topoisomerase IIalpha. PMID:16611985 Protein kinase C delta activates topoisomerase IIalpha to induce apoptotic cell death in response to DNA damage. |
| GO:0005524 ATP binding | IEA GO_REF:0000120 | ACCEPT | Summary: TOP2A binds ATP as required for its catalytic cycle. Reason: TOP2A contains an N-terminal ATPase domain and requires ATP for its strand passage mechanism. While very general, this is correct. Supporting Evidence: file:human/TOP2A/TOP2A-deep-research-openai.md The enzyme's N-terminal domain contains an ATPase motor (a member of the GHKL ATPase family). Binding of ATP at the N-terminal domains brings the dimer together and is allosterically transmitted to the DNA-gate in the core, triggering cleavage and strand passage file:human/TOP2A/TOP2A-deep-research-falcon.md The full catalytic cycle requires **ATP** (binding/hydrolysis drives conformational changes and completion of strand passage) and divalent metal ions such as **Mg2+** for DNA cleavage chemistry. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: TOP2A is predominantly nuclear. Reason: Well-established localization supported by multiple IDA studies (PMID:9155056, PMID:10959840, PMID:10788521, PMID:16611985). The deep research states 'Topo IIΞ± is predominantly a nuclear enzyme. It localizes to the cell nucleus, where the chromosomal DNA is housed'. Contains multiple nuclear localization sequences. Supporting Evidence: file:human/TOP2A/TOP2A-deep-research-openai.md Topo IIΞ± is predominantly a nuclear enzyme. It localizes to the cell nucleus, where the chromosomal DNA is housed. The protein contains multiple Nuclear Localization Sequences (NLS) in its C-terminal domain that ensure its import into the nucleus file:human/TOP2A/TOP2A-deep-research-falcon.md TOP2A is **nuclear** and becomes strongly associated with mitotic chromosomes, including enrichment along chromosome axes/scaffold, consistent with a direct role in **mitotic chromosome condensation, individualization, and segregation**. ... A mitochondrial role for TOP2 isoforms is not supported in the retrieved evidence: a systematic analysis of human topoisomerase localization/activity found **no evidence for TOP2 localization to mitochondria**. PMID:9155056 The distribution and expression of the two isoforms of DNA topoisomerase II in normal and neoplastic human tissues. PMID:10959840 DNA topoisomerase IIalpha interacts with CAD nuclease and is involved in chromatin condensation during apoptotic execution. PMID:10788521 Modulation of human DNA topoisomerase IIalpha function by interaction with 14-3-3epsilon. PMID:16611985 Protein kinase C delta activates topoisomerase IIalpha to induce apoptotic cell death in response to DNA damage. |
| GO:0005654 nucleoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: TOP2A localizes to nucleoplasm in interphase. Reason: Multiple IDA studies confirm nucleoplasmic localization (PMID:8299728, PMID:9049244, GO_REF:0000052). Also TAS evidence from Reactome pathways. This is where TOP2A functions during S-phase replication. Supporting Evidence: file:human/TOP2A/TOP2A-deep-research-openai.md In interphase cells, immunofluorescence studies show Topo IIΞ± distributed throughout the nucleus. During S-phase, Topo IIΞ± likely colocalizes with replication foci to remove supercoils and catenanes PMID:8299728 Discrete localization of different DNA topoisomerases in HeLa and K562 cell nuclei and subnuclear fractions. PMID:9049244 Cell cycle-coupled relocation of types I and II topoisomerases and modulation of catalytic enzyme activities. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Some TOP2A detected in cytoplasm. Reason: Demonstrated by IDA in PMID:9155056. While primarily nuclear, some TOP2A may be in cytoplasm during transit or in specific cell types. Less significant than nuclear localization. |
| GO:0006259 DNA metabolic process | IEA GO_REF:0000002 | ACCEPT | Summary: Very broad parent term for DNA-related processes. Reason: This is an extremely general term from IEA (InterPro-based annotation). While correct, it provides minimal information compared to more specific terms like DNA topological change or chromosome segregation. |
| GO:0006265 DNA topological change | IEA GO_REF:0000120 | ACCEPT | Summary: This is the direct biological process result of TOP2A's catalytic activity. Reason: This accurately describes what TOP2A does - it changes DNA topology by resolving supercoils and catenanes. Directly demonstrated in PMID:22323612 and confirmed throughout the literature as the core biological process mediated by the enzyme. Supporting Evidence: file:human/TOP2A/TOP2A-deep-research-openai.md Through this mechanism, TOP2A unties DNA knots, relieves supercoiling tension, and decatenates (unlinks) intertwined DNA molecules. By changing DNA linking number in steps of two, Topo IIΞ± can both relax positive/negative supercoils and untangle concatenated DNA rings file:human/TOP2A/TOP2A-deep-research-falcon.md Positive and negative supercoils**, consistent with its role in resolving torsional stress during replication/transcription and structural maintenance of chromosomes. PMID:22323612 DNA cleavage and opening reactions of human topoisomerase IIΞ± are regulated via Mg2+-mediated dynamic bending of gate-DNA. |
| GO:0016853 isomerase activity | IEA GO_REF:0000043 | ACCEPT | Summary: Topoisomerases are classified as isomerases (EC 5.x.x.x). Reason: This is the general enzyme class for topoisomerases. TOP2A is EC 5.6.2.2, which is an isomerase that changes DNA topology. This parent term is correct but very broad. |
| GO:0045870 positive regulation of single stranded viral RNA replication via double stranded DNA intermediate | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: TOP2A was shown to affect HIV-1 replication. Reason: Demonstrated in PMID:16712776 studying HIV-1 replication. This is a very specific process involving retroviruses and represents a non-core, context-specific function. The term is oddly specific for what is likely a general role of TOP2A in resolving topological stress during reverse transcription/integration. |
| GO:0046872 metal ion binding | IEA GO_REF:0000043 | ACCEPT | Summary: TOP2A binds metal ions (Mg2+) as cofactors. Reason: This is a parent term of GO:0000287 (magnesium ion binding). Both annotations are correct, with the Mg2+ term being more specific. |
| GO:0048511 rhythmic process | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: Parent term of circadian rhythm regulation. Reason: Very broad term related to GO:0042752. Peripheral to core function. |
| GO:0005515 protein binding | IPI PMID:15965487 BRCA1 participates in DNA decatenation. | REMOVE | Summary: TOP2A interacts with numerous proteins. Reason: Per curation guidelines, 'protein binding' is too vague and should be avoided. TOP2A does interact with many proteins (BRCA1, PKC, histone deacetylase, 14-3-3, p53, etc.) as documented in the many PMIDs, but the generic 'protein binding' term provides no useful functional information. More specific binding terms (like GO:0005080 protein kinase C binding) should be retained, but these generic IPI annotations should be removed. Supporting Evidence: PMID:15965487 Jun 19. BRCA1 participates in DNA decatenation. |
| GO:0005515 protein binding | IPI PMID:16611985 Protein kinase C delta activates topoisomerase IIalpha to in... | REMOVE | Summary: TOP2A interacts with numerous proteins. Reason: Per curation guidelines, 'protein binding' is too vague and should be avoided. TOP2A does interact with many proteins (BRCA1, PKC, histone deacetylase, 14-3-3, p53, etc.) as documented in the many PMIDs, but the generic 'protein binding' term provides no useful functional information. More specific binding terms (like GO:0005080 protein kinase C binding) should be retained, but these generic IPI annotations should be removed. Supporting Evidence: PMID:16611985 Protein kinase C delta activates topoisomerase IIalpha to induce apoptotic cell death in response to DNA damage. |
| GO:0005515 protein binding | IPI PMID:17983804 Functional interaction of DNA topoisomerase IIalpha with the... | REMOVE | Summary: TOP2A interacts with numerous proteins. Reason: Per curation guidelines, 'protein binding' is too vague and should be avoided. TOP2A does interact with many proteins (BRCA1, PKC, histone deacetylase, 14-3-3, p53, etc.) as documented in the many PMIDs, but the generic 'protein binding' term provides no useful functional information. More specific binding terms (like GO:0005080 protein kinase C binding) should be retained, but these generic IPI annotations should be removed. Supporting Evidence: PMID:17983804 Epub 2007 Aug 6. Functional interaction of DNA topoisomerase IIalpha with the beta-catenin and T-cell factor-4 complex. |
| GO:0005515 protein binding | IPI PMID:23698369 BAF complexes facilitate decatenation of DNA by topoisomeras... | REMOVE | Summary: TOP2A interacts with numerous proteins. Reason: Per curation guidelines, 'protein binding' is too vague and should be avoided. TOP2A does interact with many proteins (BRCA1, PKC, histone deacetylase, 14-3-3, p53, etc.) as documented in the many PMIDs, but the generic 'protein binding' term provides no useful functional information. More specific binding terms (like GO:0005080 protein kinase C binding) should be retained, but these generic IPI annotations should be removed. Supporting Evidence: PMID:23698369 BAF complexes facilitate decatenation of DNA by topoisomerase IIΞ±. |
| GO:0000775 chromosome, centromeric region | IEA GO_REF:0000107 | ACCEPT | Summary: TOP2A enriched at centromeres. Reason: IEA annotation. The deep research mentions TOP2A 'concentrate[s] along metaphase chromosome axes and at centromeric regions, which are last to be decatenated'. Centromeric localization is functionally important for final sister chromatid separation. Supporting Evidence: file:human/TOP2A/TOP2A-deep-research-openai.md As cells progress to mitosis, Topo IIΞ± becomes a component of mitotic chromosomes β it has been observed to concentrate along metaphase chromosome axes and at centromeric regions, which are last to be decatenated |
| GO:0000793 condensed chromosome | IEA GO_REF:0000107 | ACCEPT | Summary: TOP2A is a major component of condensed mitotic chromosomes. Reason: Well-supported. The deep research extensively describes TOP2A as 'a major component of the mitotic chromosome scaffold' and 'the most abundant scaffold protein by mass' on condensed chromosomes. Supporting Evidence: file:human/TOP2A/TOP2A-deep-research-openai.md Topo IIΞ± is a major component of the mitotic chromosome scaffold β scaffold proteins such as condensin complexes and kinesin KIF4A co-localize on chromatid cores, and Topo IIΞ± is the most abundant scaffold protein by mass |
| GO:0002244 hematopoietic progenitor cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: TOP2A expression in hematopoietic development. Reason: IEA annotation from Ensembl ortholog transfer. This likely reflects TOP2A's general requirement in proliferating cells rather than a specific developmental function. Any rapidly dividing hematopoietic progenitors would require TOP2A. |
| GO:0007059 chromosome segregation | IEA GO_REF:0000107 | ACCEPT | Summary: TOP2A is essential for chromosome segregation in mitosis. Reason: Core function demonstrated in multiple studies (PMID:11136718, PMID:15456904, PMID:15965487). TOP2A decatenates sister chromatids allowing them to separate during anaphase. The deep research emphasizes this is 'absolutely required' and 'essential for cell viability' in dividing cells. Supporting Evidence: file:human/TOP2A/TOP2A-deep-research-openai.md During prophase and metaphase, Topo IIΞ± localizes to chromosome axes and centromeric regions, where it resolves the last DNA catenanes holding sister chromatids together. Experimental depletion or inhibition of TOP2A prior to mitosis causes severe defects: chromosomes fail to achieve proper compaction and remain connected by DNA strands, leading to anaphase bridges or chromosome breakage file:human/TOP2A/TOP2A-deep-research-falcon.md TOP2A is tightly linked to late cell-cycle stages and mitotic progression: it is needed to remove persistent sister-chromatid entanglements to enable faithful chromosome segregation. Its activity is integrated with the **decatenation checkpoint**, and cellular outcomes after TOP2A inhibition depend on genetic context such as **p53 status**. PMID:11136718 2001 Jan 2. Deacetylase activity associates with topoisomerase II and is necessary for etoposide-induced apoptosis. PMID:15456904 2004 Sep 29. Construction, characterization, and complementation of a conditional-lethal DNA topoisomerase IIalpha mutant human cell line. PMID:15965487 Jun 19. BRCA1 participates in DNA decatenation. |
| GO:0007143 female meiotic nuclear division | IEA GO_REF:0000107 | ACCEPT | Summary: TOP2A function in female meiosis. Reason: IEA annotation from ortholog transfer (GO_REF:0000107). While specific to female meiosis, this is consistent with TOP2A's general role in chromosome segregation during cell division. Less well-characterized than mitotic roles but plausible. |
| GO:0030261 chromosome condensation | IEA GO_REF:0000107 | ACCEPT | Summary: TOP2A contributes to mitotic chromosome condensation. Reason: Well-supported. The deep research states 'Topo IIΞ± is essential for the condensation and segregation of mitotic chromosomes' and 'TOP2A becomes a component of mitotic chromosomes... contributes to the structural integrity of condensed chromosomes'. This is both a structural and enzymatic role. Falcon deep research adds that the isoform-specific C-terminal domain contributes nuclear localization and chromatin tethering important for mitotic chromosomal binding. Supporting Evidence: file:human/TOP2A/TOP2A-deep-research-openai.md Topo IIΞ± is essential for the condensation and segregation of mitotic chromosomes. Topo IIΞ± becomes a component of mitotic chromosomes and contributes to the structural integrity of condensed chromosomes. Acute degradation of Topo IIΞ± in mitotic human cells leads to aberrant chromosome morphology file:human/TOP2A/TOP2A-deep-research-falcon.md TOP2A contains an N-terminal ATPase region and a central catalytic core (tyrosine-mediated cleavage), and an isoform-specific **C-terminal domain (CTD)** that contributes to **nuclear localization and chromatin tethering**, particularly important for mitotic chromosomal binding and sister chromatid separation. |
| GO:0040016 embryonic cleavage | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: TOP2A function in early embryonic cell divisions. Reason: IEA annotation. TOP2A would be required for rapid cell divisions during embryonic cleavage, but this is a developmental context rather than a specialized function. |
| GO:0042752 regulation of circadian rhythm | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: TOP2A may play a role in circadian rhythm regulation. Reason: IEA and ISS annotations suggest a role in circadian regulation. This is mentioned in deep research but is peripheral to core function. May relate to transcriptional regulation of clock genes or cell cycle timing. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: TOP2A may affect transcription regulation. Reason: IEA annotation from ortholog data. While TOP2A can affect transcription by resolving topological stress, and has been implicated in Wnt/Ξ²-catenin signaling (PMID:35012441), direct transcriptional regulation is not a primary function. TOP2B is the main topoisomerase II isoform for transcriptional roles. Falcon deep research likewise links TOP2A to Wnt/Ξ²-catenin signaling only in a cancer/metastasis (NSCLC) context, supporting a non-core classification. Supporting Evidence: file:human/TOP2A/TOP2A-deep-research-openai.md TOP2A and TOP2B share the core mechanism but differ in regulation and context: TOP2A is cell-cycle regulated and essential for cell proliferation, whereas TOP2B is expressed more constitutively for transcriptional roles. However, in rapidly dividing cells, Topo IIΞ± likely contributes significantly to managing transcription-induced supercoils file:human/TOP2A/TOP2A-deep-research-falcon.md In **NSCLC**, TOP2A upregulation promoted migration, invasion, EMT, and survival; knockdown reduced these phenotypes, with effects tied to **Wnt/Ξ²-catenin/Wnt3a** signaling. |
| GO:0003918 DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity | IDA PMID:15491148 DNA ligation catalyzed by human topoisomerase II alpha. | ACCEPT | Summary: This is the core molecular function of TOP2A. The enzyme catalyzes ATP-dependent double-strand DNA passage to resolve topological entanglements. Reason: This correctly captures TOP2A's primary catalytic function as confirmed by biochemical assays (PMID:15491148, PMID:12711669, PMID:16611985, PMID:22323612). Supporting Evidence: file:human/TOP2A/TOP2A-deep-research-openai.md TOP2A encodes a critical enzyme that controls DNA topology. It can cut and rejoin double-stranded DNA to resolve DNA tangles and supercoils. This enzyme works as a homodimer and uses ATP hydrolysis to drive a strand-passage reaction file:human/TOP2A/TOP2A-deep-research-falcon.md TOP2A catalyzes an **ATP-dependent duplex DNA strand-passage reaction**. Mechanistically, it binds a βgateβ DNA segment (G-segment), cleaves both strands, transports a second duplex (T-segment) through the break, and then reseals the G-segment. file:human/TOP2A/TOP2A-deep-research-falcon.md A catalytic **tyrosine** performs a nucleophilic attack on the DNA phosphodiester backbone to form a **covalent 5β²-phosphotyrosyl TOP2AβDNA intermediate** (a reversible cleavage complex) that protects the DNA ends during the cycle. PMID:15491148 DNA ligation catalyzed by human topoisomerase II alpha. PMID:12711669 RNA helicase A interacts with dsDNA and topoisomerase IIalpha. PMID:16611985 Protein kinase C delta activates topoisomerase IIalpha to induce apoptotic cell death in response to DNA damage. |
| GO:0006325 chromatin organization | IMP PMID:12711669 RNA helicase A interacts with dsDNA and topoisomerase IIalph... | ACCEPT | Summary: TOP2A contributes to chromatin structure through its topoisomerase activity and scaffold role. Reason: Supported by PMID:12711669 (IMP evidence). TOP2A affects chromatin organization both through resolving topological stress and as a structural chromosome scaffold component. This is a broader term that encompasses its roles in condensation and decatenation. Supporting Evidence: file:human/TOP2A/TOP2A-deep-research-openai.md Topo IIΞ± can drive chromatin condensation via a phase-transition mechanism, requiring its CTD and ATPase activity. The CTD can mediate liquidβliquid phase separation with DNA and other proteins, and this condensation activity can modulate its catalytic function and impact chromatin organization PMID:12711669 RNA helicase A interacts with dsDNA and topoisomerase IIalpha. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: TOP2A localizes to nucleoplasm in interphase. Reason: Multiple IDA studies confirm nucleoplasmic localization (PMID:8299728, PMID:9049244, GO_REF:0000052). Also TAS evidence from Reactome pathways. This is where TOP2A functions during S-phase replication. Supporting Evidence: file:human/TOP2A/TOP2A-deep-research-openai.md In interphase cells, immunofluorescence studies show Topo IIΞ± distributed throughout the nucleus. During S-phase, Topo IIΞ± likely colocalizes with replication foci to remove supercoils and catenanes PMID:8299728 Discrete localization of different DNA topoisomerases in HeLa and K562 cell nuclei and subnuclear fractions. PMID:9049244 Cell cycle-coupled relocation of types I and II topoisomerases and modulation of catalytic enzyme activities. |
| GO:0005730 nucleolus | IDA GO_REF:0000052 | ACCEPT | Summary: TOP2A has been detected in nucleoli. Reason: Demonstrated by multiple IDA studies (PMID:8299728, PMID:9049244, PMID:9155056, PMID:17567603, GO_REF:0000052). While not the primary site of function, TOP2A is found in nucleoli, possibly related to ribosomal DNA topology. |
| GO:0005515 protein binding | IPI PMID:23213405 Taperin (c9orf75), a mutated gene in nonsyndromic deafness, ... | REMOVE | Summary: TOP2A interacts with numerous proteins. Reason: Per curation guidelines, 'protein binding' is too vague and should be avoided. TOP2A does interact with many proteins (BRCA1, PKC, histone deacetylase, 14-3-3, p53, etc.) as documented in the many PMIDs, but the generic 'protein binding' term provides no useful functional information. More specific binding terms (like GO:0005080 protein kinase C binding) should be retained, but these generic IPI annotations should be removed. Supporting Evidence: PMID:23213405 Taperin (c9orf75), a mutated gene in nonsyndromic deafness, encodes a vertebrate specific, nuclear localized protein phosphatase one alpha (PP1Ξ±) docking protein. |
| GO:0005515 protein binding | IPI PMID:36271492 The human RNA polymerase I structure reveals an HMG-like doc... | REMOVE | Summary: TOP2A interacts with numerous proteins. Reason: Per curation guidelines, 'protein binding' is too vague and should be avoided. TOP2A does interact with many proteins (BRCA1, PKC, histone deacetylase, 14-3-3, p53, etc.) as documented in the many PMIDs, but the generic 'protein binding' term provides no useful functional information. More specific binding terms (like GO:0005080 protein kinase C binding) should be retained, but these generic IPI annotations should be removed. Supporting Evidence: PMID:36271492 Print 2022 Nov. The human RNA polymerase I structure reveals an HMG-like docking domain specific to metazoans. |
| GO:0005515 protein binding | IPI PMID:10959840 DNA topoisomerase IIalpha interacts with CAD nuclease and is... | REMOVE | Summary: TOP2A interacts with numerous proteins. Reason: Per curation guidelines, 'protein binding' is too vague and should be avoided. TOP2A does interact with many proteins (BRCA1, PKC, histone deacetylase, 14-3-3, p53, etc.) as documented in the many PMIDs, but the generic 'protein binding' term provides no useful functional information. More specific binding terms (like GO:0005080 protein kinase C binding) should be retained, but these generic IPI annotations should be removed. Supporting Evidence: PMID:10959840 DNA topoisomerase IIalpha interacts with CAD nuclease and is involved in chromatin condensation during apoptotic execution. |
| GO:0005515 protein binding | IPI PMID:11062478 Histone deacetylase interacts directly with DNA topoisomeras... | REMOVE | Summary: TOP2A interacts with numerous proteins. Reason: Per curation guidelines, 'protein binding' is too vague and should be avoided. TOP2A does interact with many proteins (BRCA1, PKC, histone deacetylase, 14-3-3, p53, etc.) as documented in the many PMIDs, but the generic 'protein binding' term provides no useful functional information. More specific binding terms (like GO:0005080 protein kinase C binding) should be retained, but these generic IPI annotations should be removed. Supporting Evidence: PMID:11062478 Histone deacetylase interacts directly with DNA topoisomerase II. |
| GO:0005515 protein binding | IPI PMID:11136718 Deacetylase activity associates with topoisomerase II and is... | REMOVE | Summary: TOP2A interacts with numerous proteins. Reason: Per curation guidelines, 'protein binding' is too vague and should be avoided. TOP2A does interact with many proteins (BRCA1, PKC, histone deacetylase, 14-3-3, p53, etc.) as documented in the many PMIDs, but the generic 'protein binding' term provides no useful functional information. More specific binding terms (like GO:0005080 protein kinase C binding) should be retained, but these generic IPI annotations should be removed. Supporting Evidence: PMID:11136718 2001 Jan 2. Deacetylase activity associates with topoisomerase II and is necessary for etoposide-induced apoptosis. |
| GO:0005515 protein binding | IPI PMID:17567603 Nuclear interactions of topoisomerase II alpha and beta with... | REMOVE | Summary: TOP2A interacts with numerous proteins. Reason: Per curation guidelines, 'protein binding' is too vague and should be avoided. TOP2A does interact with many proteins (BRCA1, PKC, histone deacetylase, 14-3-3, p53, etc.) as documented in the many PMIDs, but the generic 'protein binding' term provides no useful functional information. More specific binding terms (like GO:0005080 protein kinase C binding) should be retained, but these generic IPI annotations should be removed. Supporting Evidence: PMID:17567603 Nuclear interactions of topoisomerase II alpha and beta with phospholipid scramblase 1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-4641342 | ACCEPT | Summary: TOP2A localizes to nucleoplasm in interphase. Reason: Multiple IDA studies confirm nucleoplasmic localization (PMID:8299728, PMID:9049244, GO_REF:0000052). Also TAS evidence from Reactome pathways. This is where TOP2A functions during S-phase replication. Supporting Evidence: file:human/TOP2A/TOP2A-deep-research-openai.md In interphase cells, immunofluorescence studies show Topo IIΞ± distributed throughout the nucleus. During S-phase, Topo IIΞ± likely colocalizes with replication foci to remove supercoils and catenanes PMID:8299728 Discrete localization of different DNA topoisomerases in HeLa and K562 cell nuclei and subnuclear fractions. PMID:9049244 Cell cycle-coupled relocation of types I and II topoisomerases and modulation of catalytic enzyme activities. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-4641350 | ACCEPT | Summary: TOP2A localizes to nucleoplasm in interphase. Reason: Multiple IDA studies confirm nucleoplasmic localization (PMID:8299728, PMID:9049244, GO_REF:0000052). Also TAS evidence from Reactome pathways. This is where TOP2A functions during S-phase replication. Supporting Evidence: file:human/TOP2A/TOP2A-deep-research-openai.md In interphase cells, immunofluorescence studies show Topo IIΞ± distributed throughout the nucleus. During S-phase, Topo IIΞ± likely colocalizes with replication foci to remove supercoils and catenanes PMID:8299728 Discrete localization of different DNA topoisomerases in HeLa and K562 cell nuclei and subnuclear fractions. PMID:9049244 Cell cycle-coupled relocation of types I and II topoisomerases and modulation of catalytic enzyme activities. |
| GO:0005634 nucleus | IDA PMID:9155056 The distribution and expression of the two isoforms of DNA t... | ACCEPT | Summary: TOP2A is predominantly nuclear. Reason: Well-established localization supported by multiple IDA studies (PMID:9155056, PMID:10959840, PMID:10788521, PMID:16611985). The deep research states 'Topo IIΞ± is predominantly a nuclear enzyme. It localizes to the cell nucleus, where the chromosomal DNA is housed'. Contains multiple nuclear localization sequences. Supporting Evidence: file:human/TOP2A/TOP2A-deep-research-openai.md Topo IIΞ± is predominantly a nuclear enzyme. It localizes to the cell nucleus, where the chromosomal DNA is housed. The protein contains multiple Nuclear Localization Sequences (NLS) in its C-terminal domain that ensure its import into the nucleus file:human/TOP2A/TOP2A-deep-research-falcon.md TOP2A is **nuclear** and becomes strongly associated with mitotic chromosomes, including enrichment along chromosome axes/scaffold, consistent with a direct role in **mitotic chromosome condensation, individualization, and segregation**. ... A mitochondrial role for TOP2 isoforms is not supported in the retrieved evidence: a systematic analysis of human topoisomerase localization/activity found **no evidence for TOP2 localization to mitochondria**. PMID:9155056 The distribution and expression of the two isoforms of DNA topoisomerase II in normal and neoplastic human tissues. PMID:10959840 DNA topoisomerase IIalpha interacts with CAD nuclease and is involved in chromatin condensation during apoptotic execution. PMID:10788521 Modulation of human DNA topoisomerase IIalpha function by interaction with 14-3-3epsilon. PMID:16611985 Protein kinase C delta activates topoisomerase IIalpha to induce apoptotic cell death in response to DNA damage. |
| GO:0005654 nucleoplasm | IDA PMID:8299728 Discrete localization of different DNA topoisomerases in HeL... | ACCEPT | Summary: TOP2A localizes to nucleoplasm in interphase. Reason: Multiple IDA studies confirm nucleoplasmic localization (PMID:8299728, PMID:9049244, GO_REF:0000052). Also TAS evidence from Reactome pathways. This is where TOP2A functions during S-phase replication. Supporting Evidence: file:human/TOP2A/TOP2A-deep-research-openai.md In interphase cells, immunofluorescence studies show Topo IIΞ± distributed throughout the nucleus. During S-phase, Topo IIΞ± likely colocalizes with replication foci to remove supercoils and catenanes PMID:8299728 Discrete localization of different DNA topoisomerases in HeLa and K562 cell nuclei and subnuclear fractions. PMID:9049244 Cell cycle-coupled relocation of types I and II topoisomerases and modulation of catalytic enzyme activities. |
| GO:0005730 nucleolus | IDA PMID:8299728 Discrete localization of different DNA topoisomerases in HeL... | ACCEPT | Summary: TOP2A has been detected in nucleoli. Reason: Demonstrated by multiple IDA studies (PMID:8299728, PMID:9049244, PMID:9155056, PMID:17567603, GO_REF:0000052). While not the primary site of function, TOP2A is found in nucleoli, possibly related to ribosomal DNA topology. Supporting Evidence: PMID:8299728 Discrete localization of different DNA topoisomerases in HeLa and K562 cell nuclei and subnuclear fractions. |
| GO:0005730 nucleolus | IDA PMID:9155056 The distribution and expression of the two isoforms of DNA t... | ACCEPT | Summary: TOP2A has been detected in nucleoli. Reason: Demonstrated by multiple IDA studies (PMID:8299728, PMID:9049244, PMID:9155056, PMID:17567603, GO_REF:0000052). While not the primary site of function, TOP2A is found in nucleoli, possibly related to ribosomal DNA topology. Supporting Evidence: PMID:9155056 The distribution and expression of the two isoforms of DNA topoisomerase II in normal and neoplastic human tissues. |
| GO:0005737 cytoplasm | IDA PMID:9155056 The distribution and expression of the two isoforms of DNA t... | ACCEPT | Summary: Some TOP2A detected in cytoplasm. Reason: Demonstrated by IDA in PMID:9155056. While primarily nuclear, some TOP2A may be in cytoplasm during transit or in specific cell types. Less significant than nuclear localization. Supporting Evidence: PMID:9155056 The distribution and expression of the two isoforms of DNA topoisomerase II in normal and neoplastic human tissues. |
| GO:0005515 protein binding | IPI PMID:26030138 Identification of Novel Proteins Co-Purifying with Cockayne ... | REMOVE | Summary: TOP2A interacts with numerous proteins. Reason: Per curation guidelines, 'protein binding' is too vague and should be avoided. TOP2A does interact with many proteins (BRCA1, PKC, histone deacetylase, 14-3-3, p53, etc.) as documented in the many PMIDs, but the generic 'protein binding' term provides no useful functional information. More specific binding terms (like GO:0005080 protein kinase C binding) should be retained, but these generic IPI annotations should be removed. Supporting Evidence: PMID:26030138 eCollection 2015. Identification of Novel Proteins Co-Purifying with Cockayne Syndrome Group B (CSB) Reveals Potential Roles for CSB in RNA Metabolism and Chromatin Dynamics. |
| GO:0005515 protein binding | IPI PMID:23652018 GANP regulates recruitment of AID to immunoglobulin variable... | REMOVE | Summary: TOP2A interacts with numerous proteins. Reason: Per curation guidelines, 'protein binding' is too vague and should be avoided. TOP2A does interact with many proteins (BRCA1, PKC, histone deacetylase, 14-3-3, p53, etc.) as documented in the many PMIDs, but the generic 'protein binding' term provides no useful functional information. More specific binding terms (like GO:0005080 protein kinase C binding) should be retained, but these generic IPI annotations should be removed. Supporting Evidence: PMID:23652018 GANP regulates recruitment of AID to immunoglobulin variable regions by modulating transcription and nucleosome occupancy. |
| GO:0003918 DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity | IMP PMID:12711669 RNA helicase A interacts with dsDNA and topoisomerase IIalph... | ACCEPT | Summary: This is the core molecular function of TOP2A. The enzyme catalyzes ATP-dependent double-strand DNA passage to resolve topological entanglements. Reason: This correctly captures TOP2A's primary catalytic function as confirmed by biochemical assays (PMID:15491148, PMID:12711669, PMID:16611985, PMID:22323612). Supporting Evidence: file:human/TOP2A/TOP2A-deep-research-openai.md TOP2A encodes a critical enzyme that controls DNA topology. It can cut and rejoin double-stranded DNA to resolve DNA tangles and supercoils. This enzyme works as a homodimer and uses ATP hydrolysis to drive a strand-passage reaction file:human/TOP2A/TOP2A-deep-research-falcon.md TOP2A catalyzes an **ATP-dependent duplex DNA strand-passage reaction**. Mechanistically, it binds a βgateβ DNA segment (G-segment), cleaves both strands, transports a second duplex (T-segment) through the break, and then reseals the G-segment. file:human/TOP2A/TOP2A-deep-research-falcon.md A catalytic **tyrosine** performs a nucleophilic attack on the DNA phosphodiester backbone to form a **covalent 5β²-phosphotyrosyl TOP2AβDNA intermediate** (a reversible cleavage complex) that protects the DNA ends during the cycle. PMID:15491148 DNA ligation catalyzed by human topoisomerase II alpha. PMID:12711669 RNA helicase A interacts with dsDNA and topoisomerase IIalpha. PMID:16611985 Protein kinase C delta activates topoisomerase IIalpha to induce apoptotic cell death in response to DNA damage. |
| GO:0005515 protein binding | IPI PMID:12711669 RNA helicase A interacts with dsDNA and topoisomerase IIalph... | REMOVE | Summary: TOP2A interacts with numerous proteins. Reason: Per curation guidelines, 'protein binding' is too vague and should be avoided. TOP2A does interact with many proteins (BRCA1, PKC, histone deacetylase, 14-3-3, p53, etc.) as documented in the many PMIDs, but the generic 'protein binding' term provides no useful functional information. More specific binding terms (like GO:0005080 protein kinase C binding) should be retained, but these generic IPI annotations should be removed. Supporting Evidence: PMID:12711669 RNA helicase A interacts with dsDNA and topoisomerase IIalpha. |
| GO:1990904 ribonucleoprotein complex | IDA PMID:12711669 RNA helicase A interacts with dsDNA and topoisomerase IIalph... | ACCEPT | Summary: TOP2A found in ribonucleoprotein complexes. Reason: Demonstrated in PMID:12711669 showing interaction with RNA helicase A (DHX9). This may reflect functional interactions during transcription or RNA processing. Supporting Evidence: PMID:12711669 RNA helicase A interacts with dsDNA and topoisomerase IIalpha. |
| GO:0042752 regulation of circadian rhythm | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: TOP2A may play a role in circadian rhythm regulation. Reason: IEA and ISS annotations suggest a role in circadian regulation. This is mentioned in deep research but is peripheral to core function. May relate to transcriptional regulation of clock genes or cell cycle timing. |
| GO:0005515 protein binding | IPI PMID:18790802 The SET and transposase domain protein Metnase enhances chro... | REMOVE | Summary: TOP2A interacts with numerous proteins. Reason: Per curation guidelines, 'protein binding' is too vague and should be avoided. TOP2A does interact with many proteins (BRCA1, PKC, histone deacetylase, 14-3-3, p53, etc.) as documented in the many PMIDs, but the generic 'protein binding' term provides no useful functional information. More specific binding terms (like GO:0005080 protein kinase C binding) should be retained, but these generic IPI annotations should be removed. Supporting Evidence: PMID:18790802 Sep 12. The SET and transposase domain protein Metnase enhances chromosome decatenation: regulation by automethylation. |
| GO:0005515 protein binding | IPI PMID:20457750 Metnase promotes restart and repair of stalled and collapsed... | REMOVE | Summary: TOP2A interacts with numerous proteins. Reason: Per curation guidelines, 'protein binding' is too vague and should be avoided. TOP2A does interact with many proteins (BRCA1, PKC, histone deacetylase, 14-3-3, p53, etc.) as documented in the many PMIDs, but the generic 'protein binding' term provides no useful functional information. More specific binding terms (like GO:0005080 protein kinase C binding) should be retained, but these generic IPI annotations should be removed. Supporting Evidence: PMID:20457750 May 10. Metnase promotes restart and repair of stalled and collapsed replication forks. |
| GO:0032991 protein-containing complex | IDA PMID:16611985 Protein kinase C delta activates topoisomerase IIalpha to in... | ACCEPT | Summary: TOP2A is found in protein complexes. Reason: Demonstrated in PMID:16611985. This is very general but correct - TOP2A interacts with many proteins and is part of various complexes (e.g., with DHX9, condensins, etc.). Supporting Evidence: PMID:16611985 Protein kinase C delta activates topoisomerase IIalpha to induce apoptotic cell death in response to DNA damage. |
| GO:0003723 RNA binding | HDA PMID:22681889 The mRNA-bound proteome and its global occupancy profile on ... | ACCEPT | Summary: TOP2A was identified in RNA-binding proteome studies. Reason: Identified by HDA (high-throughput direct assay) in PMID:22681889. TOP2A was found in mRNA-bound proteome. While not a primary function, this may reflect associations in ribonucleoprotein complexes or non-canonical roles. Supporting Evidence: GO_REF:0000052 Identified in high-throughput mRNA-bound proteome study PMID:22681889 The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts. |
| GO:0000287 magnesium ion binding | IDA PMID:22323612 DNA cleavage and opening reactions of human topoisomerase II... | ACCEPT | Summary: Mg2+ is a cofactor required for TOP2A's DNA cleavage activity. Reason: Directly demonstrated in PMID:22323612. Mg2+ ions are essential cofactors for the DNA cleavage reaction and regulate the enzyme's mechanism. Supporting Evidence: PMID:22323612 DNA cleavage and opening reactions of human topoisomerase IIΞ± are regulated via Mg2+-mediated dynamic bending of gate-DNA file:human/TOP2A/TOP2A-deep-research-falcon.md The full catalytic cycle requires **ATP** (binding/hydrolysis drives conformational changes and completion of strand passage) and divalent metal ions such as **Mg2+** for DNA cleavage chemistry. |
| GO:0006265 DNA topological change | IDA PMID:22323612 DNA cleavage and opening reactions of human topoisomerase II... | ACCEPT | Summary: This is the direct biological process result of TOP2A's catalytic activity. Reason: This accurately describes what TOP2A does - it changes DNA topology by resolving supercoils and catenanes. Directly demonstrated in PMID:22323612 and confirmed throughout the literature as the core biological process mediated by the enzyme. Supporting Evidence: file:human/TOP2A/TOP2A-deep-research-openai.md Through this mechanism, TOP2A unties DNA knots, relieves supercoiling tension, and decatenates (unlinks) intertwined DNA molecules. By changing DNA linking number in steps of two, Topo IIΞ± can both relax positive/negative supercoils and untangle concatenated DNA rings file:human/TOP2A/TOP2A-deep-research-falcon.md Positive and negative supercoils**, consistent with its role in resolving torsional stress during replication/transcription and structural maintenance of chromosomes. PMID:22323612 DNA cleavage and opening reactions of human topoisomerase IIΞ± are regulated via Mg2+-mediated dynamic bending of gate-DNA. |
| GO:0008301 DNA binding, bending | IDA PMID:22323612 DNA cleavage and opening reactions of human topoisomerase II... | ACCEPT | Summary: TOP2A bends DNA as part of its catalytic mechanism. Reason: Directly demonstrated in PMID:22323612, which showed that 'DNA cleavage and opening reactions of human topoisomerase IIΞ± are regulated via Mg2+-mediated dynamic bending of gate-DNA'. This bending is mechanistically important for the strand passage reaction. Supporting Evidence: PMID:22323612 DNA cleavage and opening reactions of human topoisomerase IIΞ± are regulated via Mg2+-mediated dynamic bending of gate-DNA |
| GO:0005515 protein binding | IPI PMID:19390626 Metnase mediates resistance to topoisomerase II inhibitors i... | REMOVE | Summary: TOP2A interacts with numerous proteins. Reason: Per curation guidelines, 'protein binding' is too vague and should be avoided. TOP2A does interact with many proteins (BRCA1, PKC, histone deacetylase, 14-3-3, p53, etc.) as documented in the many PMIDs, but the generic 'protein binding' term provides no useful functional information. More specific binding terms (like GO:0005080 protein kinase C binding) should be retained, but these generic IPI annotations should be removed. Supporting Evidence: PMID:19390626 Metnase mediates resistance to topoisomerase II inhibitors in breast cancer cells. |
| GO:0005730 nucleolus | IDA PMID:17567603 Nuclear interactions of topoisomerase II alpha and beta with... | ACCEPT | Summary: TOP2A has been detected in nucleoli. Reason: Demonstrated by multiple IDA studies (PMID:8299728, PMID:9049244, PMID:9155056, PMID:17567603, GO_REF:0000052). While not the primary site of function, TOP2A is found in nucleoli, possibly related to ribosomal DNA topology. Supporting Evidence: PMID:17567603 Nuclear interactions of topoisomerase II alpha and beta with phospholipid scramblase 1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8964531 | ACCEPT | Summary: TOP2A localizes to nucleoplasm in interphase. Reason: Multiple IDA studies confirm nucleoplasmic localization (PMID:8299728, PMID:9049244, GO_REF:0000052). Also TAS evidence from Reactome pathways. This is where TOP2A functions during S-phase replication. Supporting Evidence: file:human/TOP2A/TOP2A-deep-research-openai.md In interphase cells, immunofluorescence studies show Topo IIΞ± distributed throughout the nucleus. During S-phase, Topo IIΞ± likely colocalizes with replication foci to remove supercoils and catenanes PMID:8299728 Discrete localization of different DNA topoisomerases in HeLa and K562 cell nuclei and subnuclear fractions. PMID:9049244 Cell cycle-coupled relocation of types I and II topoisomerases and modulation of catalytic enzyme activities. |
| GO:0000228 nuclear chromosome | IDA PMID:9049244 Cell cycle-coupled relocation of types I and II topoisomeras... | ACCEPT | Summary: TOP2A associates with nuclear chromosomes. Reason: Demonstrated in PMID:9049244. This is accurate - TOP2A binds to chromosomes particularly during mitosis when it is a major scaffold component. Supporting Evidence: PMID:9049244 Cell cycle-coupled relocation of types I and II topoisomerases and modulation of catalytic enzyme activities. |
| GO:0005634 nucleus | IDA PMID:10959840 DNA topoisomerase IIalpha interacts with CAD nuclease and is... | ACCEPT | Summary: TOP2A is predominantly nuclear. Reason: Well-established localization supported by multiple IDA studies (PMID:9155056, PMID:10959840, PMID:10788521, PMID:16611985). The deep research states 'Topo IIΞ± is predominantly a nuclear enzyme. It localizes to the cell nucleus, where the chromosomal DNA is housed'. Contains multiple nuclear localization sequences. Supporting Evidence: file:human/TOP2A/TOP2A-deep-research-openai.md Topo IIΞ± is predominantly a nuclear enzyme. It localizes to the cell nucleus, where the chromosomal DNA is housed. The protein contains multiple Nuclear Localization Sequences (NLS) in its C-terminal domain that ensure its import into the nucleus file:human/TOP2A/TOP2A-deep-research-falcon.md TOP2A is **nuclear** and becomes strongly associated with mitotic chromosomes, including enrichment along chromosome axes/scaffold, consistent with a direct role in **mitotic chromosome condensation, individualization, and segregation**. ... A mitochondrial role for TOP2 isoforms is not supported in the retrieved evidence: a systematic analysis of human topoisomerase localization/activity found **no evidence for TOP2 localization to mitochondria**. PMID:9155056 The distribution and expression of the two isoforms of DNA topoisomerase II in normal and neoplastic human tissues. PMID:10959840 DNA topoisomerase IIalpha interacts with CAD nuclease and is involved in chromatin condensation during apoptotic execution. PMID:10788521 Modulation of human DNA topoisomerase IIalpha function by interaction with 14-3-3epsilon. PMID:16611985 Protein kinase C delta activates topoisomerase IIalpha to induce apoptotic cell death in response to DNA damage. |
| GO:0007059 chromosome segregation | IMP PMID:11136718 Deacetylase activity associates with topoisomerase II and is... | ACCEPT | Summary: TOP2A is essential for chromosome segregation in mitosis. Reason: Core function demonstrated in multiple studies (PMID:11136718, PMID:15456904, PMID:15965487). TOP2A decatenates sister chromatids allowing them to separate during anaphase. The deep research emphasizes this is 'absolutely required' and 'essential for cell viability' in dividing cells. Supporting Evidence: file:human/TOP2A/TOP2A-deep-research-openai.md During prophase and metaphase, Topo IIΞ± localizes to chromosome axes and centromeric regions, where it resolves the last DNA catenanes holding sister chromatids together. Experimental depletion or inhibition of TOP2A prior to mitosis causes severe defects: chromosomes fail to achieve proper compaction and remain connected by DNA strands, leading to anaphase bridges or chromosome breakage file:human/TOP2A/TOP2A-deep-research-falcon.md TOP2A is tightly linked to late cell-cycle stages and mitotic progression: it is needed to remove persistent sister-chromatid entanglements to enable faithful chromosome segregation. Its activity is integrated with the **decatenation checkpoint**, and cellular outcomes after TOP2A inhibition depend on genetic context such as **p53 status**. PMID:11136718 2001 Jan 2. Deacetylase activity associates with topoisomerase II and is necessary for etoposide-induced apoptosis. PMID:15456904 2004 Sep 29. Construction, characterization, and complementation of a conditional-lethal DNA topoisomerase IIalpha mutant human cell line. PMID:15965487 Jun 19. BRCA1 participates in DNA decatenation. |
| GO:0009330 DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) complex | IDA PMID:10473615 Using a biochemical approach to identify the primary dimeriz... | ACCEPT | Summary: TOP2A forms a dimeric complex. Reason: Demonstrated in PMID:10473615. TOP2A functions as a homodimeric complex, which is the active form of the enzyme. Supporting Evidence: PMID:10473615 Using a biochemical approach to identify the primary dimerization regions in human DNA topoisomerase IIalpha. |
| GO:0030263 apoptotic chromosome condensation | IDA PMID:10959840 DNA topoisomerase IIalpha interacts with CAD nuclease and is... | ACCEPT | Summary: TOP2A is involved in chromosome condensation during apoptosis. Reason: Demonstrated in PMID:10959840, which showed 'DNA topoisomerase IIΞ± interacts with CAD nuclease and is involved in chromatin condensation during apoptotic execution'. This is a specific role in apoptosis. Supporting Evidence: PMID:10959840 DNA topoisomerase IIΞ± interacts with CAD nuclease and is involved in chromatin condensation during apoptotic execution |
| GO:0003677 DNA binding | IDA PMID:12079377 The ATP-operated clamp of human DNA topoisomerase IIalpha: h... | ACCEPT | Summary: TOP2A binds DNA as part of its mechanism, but this is too general for the core function. Reason: TOP2A does bind DNA directly as confirmed by biochemical studies (PMID:12079377, PMID:10788521, PMID:9049244, PMID:22323612). However, this is a very general molecular function term. The enzyme's DNA binding is integral to its topoisomerase activity, and this annotation provides useful but non-specific information about the protein's molecular capabilities. Supporting Evidence: PMID:22323612 DNA cleavage and opening reactions of human topoisomerase IIΞ± are regulated via Mg2+-mediated dynamic bending of gate-DNA PMID:12079377 The ATP-operated clamp of human DNA topoisomerase IIalpha: hyperstimulation of ATPase by "piggy-back" binding. PMID:10788521 Modulation of human DNA topoisomerase IIalpha function by interaction with 14-3-3epsilon. PMID:9049244 Cell cycle-coupled relocation of types I and II topoisomerases and modulation of catalytic enzyme activities. |
| GO:0008094 ATP-dependent activity, acting on DNA | IDA PMID:12079377 The ATP-operated clamp of human DNA topoisomerase IIalpha: h... | ACCEPT | Summary: TOP2A's catalytic activity is ATP-dependent. Reason: Correct and supported by PMID:12079377. This is a broader term than GO:0003918 but accurately describes the ATP-dependent nature of TOP2A's DNA manipulation activity. The enzyme uses ATP hydrolysis to drive conformational changes needed for strand passage. Supporting Evidence: file:human/TOP2A/TOP2A-deep-research-openai.md This ATP-dependent double-strand passage reaction is the hallmark of Topo IIΞ±'s catalytic function. Each Topo IIΞ± monomer contributes an active-site tyrosine that cleaves one strand of the DNA duplex. The enzyme dimer then undergoes a large conformational change (powered by ATP binding and hydrolysis) PMID:12079377 The ATP-operated clamp of human DNA topoisomerase IIalpha: hyperstimulation of ATPase by "piggy-back" binding. |
| GO:0003677 DNA binding | IDA PMID:10788521 Modulation of human DNA topoisomerase IIalpha function by in... | ACCEPT | Summary: TOP2A binds DNA as part of its mechanism, but this is too general for the core function. Reason: TOP2A does bind DNA directly as confirmed by biochemical studies (PMID:12079377, PMID:10788521, PMID:9049244, PMID:22323612). However, this is a very general molecular function term. The enzyme's DNA binding is integral to its topoisomerase activity, and this annotation provides useful but non-specific information about the protein's molecular capabilities. Supporting Evidence: PMID:22323612 DNA cleavage and opening reactions of human topoisomerase IIΞ± are regulated via Mg2+-mediated dynamic bending of gate-DNA PMID:12079377 The ATP-operated clamp of human DNA topoisomerase IIalpha: hyperstimulation of ATPase by "piggy-back" binding. PMID:10788521 Modulation of human DNA topoisomerase IIalpha function by interaction with 14-3-3epsilon. PMID:9049244 Cell cycle-coupled relocation of types I and II topoisomerases and modulation of catalytic enzyme activities. |
| GO:0005515 protein binding | IPI PMID:10666337 Human topoisomerase IIalpha and IIbeta interact with the C-t... | REMOVE | Summary: TOP2A interacts with numerous proteins. Reason: Per curation guidelines, 'protein binding' is too vague and should be avoided. TOP2A does interact with many proteins (BRCA1, PKC, histone deacetylase, 14-3-3, p53, etc.) as documented in the many PMIDs, but the generic 'protein binding' term provides no useful functional information. More specific binding terms (like GO:0005080 protein kinase C binding) should be retained, but these generic IPI annotations should be removed. Supporting Evidence: PMID:10666337 Human topoisomerase IIalpha and IIbeta interact with the C-terminal region of p53. |
| GO:0005515 protein binding | IPI PMID:10788521 Modulation of human DNA topoisomerase IIalpha function by in... | REMOVE | Summary: TOP2A interacts with numerous proteins. Reason: Per curation guidelines, 'protein binding' is too vague and should be avoided. TOP2A does interact with many proteins (BRCA1, PKC, histone deacetylase, 14-3-3, p53, etc.) as documented in the many PMIDs, but the generic 'protein binding' term provides no useful functional information. More specific binding terms (like GO:0005080 protein kinase C binding) should be retained, but these generic IPI annotations should be removed. Supporting Evidence: PMID:10788521 Modulation of human DNA topoisomerase IIalpha function by interaction with 14-3-3epsilon. |
| GO:0005634 nucleus | IDA PMID:10788521 Modulation of human DNA topoisomerase IIalpha function by in... | ACCEPT | Summary: TOP2A is predominantly nuclear. Reason: Well-established localization supported by multiple IDA studies (PMID:9155056, PMID:10959840, PMID:10788521, PMID:16611985). The deep research states 'Topo IIΞ± is predominantly a nuclear enzyme. It localizes to the cell nucleus, where the chromosomal DNA is housed'. Contains multiple nuclear localization sequences. Supporting Evidence: file:human/TOP2A/TOP2A-deep-research-openai.md Topo IIΞ± is predominantly a nuclear enzyme. It localizes to the cell nucleus, where the chromosomal DNA is housed. The protein contains multiple Nuclear Localization Sequences (NLS) in its C-terminal domain that ensure its import into the nucleus file:human/TOP2A/TOP2A-deep-research-falcon.md TOP2A is **nuclear** and becomes strongly associated with mitotic chromosomes, including enrichment along chromosome axes/scaffold, consistent with a direct role in **mitotic chromosome condensation, individualization, and segregation**. ... A mitochondrial role for TOP2 isoforms is not supported in the retrieved evidence: a systematic analysis of human topoisomerase localization/activity found **no evidence for TOP2 localization to mitochondria**. PMID:9155056 The distribution and expression of the two isoforms of DNA topoisomerase II in normal and neoplastic human tissues. PMID:10959840 DNA topoisomerase IIalpha interacts with CAD nuclease and is involved in chromatin condensation during apoptotic execution. PMID:10788521 Modulation of human DNA topoisomerase IIalpha function by interaction with 14-3-3epsilon. PMID:16611985 Protein kinase C delta activates topoisomerase IIalpha to induce apoptotic cell death in response to DNA damage. |
| GO:0007059 chromosome segregation | IMP PMID:15456904 Construction, characterization, and complementation of a con... | ACCEPT | Summary: TOP2A is essential for chromosome segregation in mitosis. Reason: Core function demonstrated in multiple studies (PMID:11136718, PMID:15456904, PMID:15965487). TOP2A decatenates sister chromatids allowing them to separate during anaphase. The deep research emphasizes this is 'absolutely required' and 'essential for cell viability' in dividing cells. Supporting Evidence: file:human/TOP2A/TOP2A-deep-research-openai.md During prophase and metaphase, Topo IIΞ± localizes to chromosome axes and centromeric regions, where it resolves the last DNA catenanes holding sister chromatids together. Experimental depletion or inhibition of TOP2A prior to mitosis causes severe defects: chromosomes fail to achieve proper compaction and remain connected by DNA strands, leading to anaphase bridges or chromosome breakage file:human/TOP2A/TOP2A-deep-research-falcon.md TOP2A is tightly linked to late cell-cycle stages and mitotic progression: it is needed to remove persistent sister-chromatid entanglements to enable faithful chromosome segregation. Its activity is integrated with the **decatenation checkpoint**, and cellular outcomes after TOP2A inhibition depend on genetic context such as **p53 status**. PMID:11136718 2001 Jan 2. Deacetylase activity associates with topoisomerase II and is necessary for etoposide-induced apoptosis. PMID:15456904 2004 Sep 29. Construction, characterization, and complementation of a conditional-lethal DNA topoisomerase IIalpha mutant human cell line. PMID:15965487 Jun 19. BRCA1 participates in DNA decatenation. |
| GO:0042803 protein homodimerization activity | IPI PMID:10473615 Using a biochemical approach to identify the primary dimeriz... | ACCEPT | Summary: TOP2A functions as a homodimer. Reason: Well-established that TOP2A operates as a homodimer. PMID:10473615 specifically identified dimerization regions. The deep research states 'This enzyme works as a homodimer' and 'The enzyme operates as a dimeric molecular clamp'. Supporting Evidence: file:human/TOP2A/TOP2A-deep-research-openai.md This enzyme works as a homodimer. The enzyme operates as a dimeric molecular clamp. Each Topo IIΞ± monomer contributes an active-site tyrosine that cleaves one strand of the DNA duplex PMID:10473615 Using a biochemical approach to identify the primary dimerization regions in human DNA topoisomerase IIalpha. |
| GO:0045870 positive regulation of single stranded viral RNA replication via double stranded DNA intermediate | IMP PMID:16712776 A study of the topoisomerase II activity in HIV-1 replicatio... | KEEP AS NON CORE | Summary: TOP2A was shown to affect HIV-1 replication. Reason: Demonstrated in PMID:16712776 studying HIV-1 replication. This is a very specific process involving retroviruses and represents a non-core, context-specific function. The term is oddly specific for what is likely a general role of TOP2A in resolving topological stress during reverse transcription/integration. Supporting Evidence: PMID:16712776 A study of the topoisomerase II activity in HIV-1 replication using the ferrocene derivatives as probes. |
| GO:0046982 protein heterodimerization activity | IPI PMID:10473615 Using a biochemical approach to identify the primary dimeriz... | ACCEPT | Summary: TOP2A can form heterodimers with TOP2B or truncated isoforms. Reason: Supported by PMID:10473615. While TOP2A primarily functions as a homodimer, it can heterodimerize with TOP2B or with truncated isoforms, which is relevant for some cellular contexts and drug resistance mechanisms. Supporting Evidence: PMID:10473615 Using a biochemical approach to identify the primary dimerization regions in human DNA topoisomerase IIalpha. |
| GO:0003677 DNA binding | IDA PMID:9049244 Cell cycle-coupled relocation of types I and II topoisomeras... | ACCEPT | Summary: TOP2A binds DNA as part of its mechanism, but this is too general for the core function. Reason: TOP2A does bind DNA directly as confirmed by biochemical studies (PMID:12079377, PMID:10788521, PMID:9049244, PMID:22323612). However, this is a very general molecular function term. The enzyme's DNA binding is integral to its topoisomerase activity, and this annotation provides useful but non-specific information about the protein's molecular capabilities. Supporting Evidence: PMID:22323612 DNA cleavage and opening reactions of human topoisomerase IIΞ± are regulated via Mg2+-mediated dynamic bending of gate-DNA PMID:12079377 The ATP-operated clamp of human DNA topoisomerase IIalpha: hyperstimulation of ATPase by "piggy-back" binding. PMID:10788521 Modulation of human DNA topoisomerase IIalpha function by interaction with 14-3-3epsilon. PMID:9049244 Cell cycle-coupled relocation of types I and II topoisomerases and modulation of catalytic enzyme activities. |
| GO:0003682 chromatin binding | IDA PMID:9049244 Cell cycle-coupled relocation of types I and II topoisomeras... | ACCEPT | Summary: TOP2A binds chromatin, especially during mitosis when it is a major chromosome scaffold component. Reason: Well-supported by experimental evidence (PMID:9049244). The deep research emphasizes that 'Topo IIΞ± is a major component of the mitotic chromosome scaffold' and 'proteomic analyses of isolated human chromosomes identified Topo IIΞ± as a major scaffold protein'. This binding is functionally important for chromosome structure. Supporting Evidence: file:human/TOP2A/TOP2A-deep-research-openai.md Topo IIΞ± is a major component of the mitotic chromosome scaffold. Proteomic analyses of isolated human chromosomes identified Topo IIΞ± as a major scaffold protein that remains bound after high-salt extractions, consistent with an architectural role file:human/TOP2A/TOP2A-deep-research-falcon.md TOP2A is **nuclear** and becomes strongly associated with mitotic chromosomes, including enrichment along chromosome axes/scaffold, consistent with a direct role in **mitotic chromosome condensation, individualization, and segregation**. PMID:9049244 Cell cycle-coupled relocation of types I and II topoisomerases and modulation of catalytic enzyme activities. |
| GO:0003918 DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity | IDA PMID:16611985 Protein kinase C delta activates topoisomerase IIalpha to in... | ACCEPT | Summary: This is the core molecular function of TOP2A. The enzyme catalyzes ATP-dependent double-strand DNA passage to resolve topological entanglements. Reason: This correctly captures TOP2A's primary catalytic function as confirmed by biochemical assays (PMID:15491148, PMID:12711669, PMID:16611985, PMID:22323612). Supporting Evidence: file:human/TOP2A/TOP2A-deep-research-openai.md TOP2A encodes a critical enzyme that controls DNA topology. It can cut and rejoin double-stranded DNA to resolve DNA tangles and supercoils. This enzyme works as a homodimer and uses ATP hydrolysis to drive a strand-passage reaction file:human/TOP2A/TOP2A-deep-research-falcon.md TOP2A catalyzes an **ATP-dependent duplex DNA strand-passage reaction**. Mechanistically, it binds a βgateβ DNA segment (G-segment), cleaves both strands, transports a second duplex (T-segment) through the break, and then reseals the G-segment. file:human/TOP2A/TOP2A-deep-research-falcon.md A catalytic **tyrosine** performs a nucleophilic attack on the DNA phosphodiester backbone to form a **covalent 5β²-phosphotyrosyl TOP2AβDNA intermediate** (a reversible cleavage complex) that protects the DNA ends during the cycle. PMID:15491148 DNA ligation catalyzed by human topoisomerase II alpha. PMID:12711669 RNA helicase A interacts with dsDNA and topoisomerase IIalpha. PMID:16611985 Protein kinase C delta activates topoisomerase IIalpha to induce apoptotic cell death in response to DNA damage. |
| GO:0005080 protein kinase C binding | IPI PMID:16611985 Protein kinase C delta activates topoisomerase IIalpha to in... | ACCEPT | Summary: TOP2A interacts with protein kinase C. Reason: Demonstrated in PMID:16611985, which showed that 'Protein kinase C delta activates topoisomerase IIΞ± to induce apoptotic cell death in response to DNA damage'. This interaction is functionally relevant for regulation. Supporting Evidence: PMID:16611985 Protein kinase C delta activates topoisomerase IIΞ± to induce apoptotic cell death in response to DNA damage |
| GO:0005634 nucleus | IDA PMID:16611985 Protein kinase C delta activates topoisomerase IIalpha to in... | ACCEPT | Summary: TOP2A is predominantly nuclear. Reason: Well-established localization supported by multiple IDA studies (PMID:9155056, PMID:10959840, PMID:10788521, PMID:16611985). The deep research states 'Topo IIΞ± is predominantly a nuclear enzyme. It localizes to the cell nucleus, where the chromosomal DNA is housed'. Contains multiple nuclear localization sequences. Supporting Evidence: file:human/TOP2A/TOP2A-deep-research-openai.md Topo IIΞ± is predominantly a nuclear enzyme. It localizes to the cell nucleus, where the chromosomal DNA is housed. The protein contains multiple Nuclear Localization Sequences (NLS) in its C-terminal domain that ensure its import into the nucleus file:human/TOP2A/TOP2A-deep-research-falcon.md TOP2A is **nuclear** and becomes strongly associated with mitotic chromosomes, including enrichment along chromosome axes/scaffold, consistent with a direct role in **mitotic chromosome condensation, individualization, and segregation**. ... A mitochondrial role for TOP2 isoforms is not supported in the retrieved evidence: a systematic analysis of human topoisomerase localization/activity found **no evidence for TOP2 localization to mitochondria**. PMID:9155056 The distribution and expression of the two isoforms of DNA topoisomerase II in normal and neoplastic human tissues. PMID:10959840 DNA topoisomerase IIalpha interacts with CAD nuclease and is involved in chromatin condensation during apoptotic execution. PMID:10788521 Modulation of human DNA topoisomerase IIalpha function by interaction with 14-3-3epsilon. PMID:16611985 Protein kinase C delta activates topoisomerase IIalpha to induce apoptotic cell death in response to DNA damage. |
| GO:0005654 nucleoplasm | IDA PMID:9049244 Cell cycle-coupled relocation of types I and II topoisomeras... | ACCEPT | Summary: TOP2A localizes to nucleoplasm in interphase. Reason: Multiple IDA studies confirm nucleoplasmic localization (PMID:8299728, PMID:9049244, GO_REF:0000052). Also TAS evidence from Reactome pathways. This is where TOP2A functions during S-phase replication. Supporting Evidence: file:human/TOP2A/TOP2A-deep-research-openai.md In interphase cells, immunofluorescence studies show Topo IIΞ± distributed throughout the nucleus. During S-phase, Topo IIΞ± likely colocalizes with replication foci to remove supercoils and catenanes PMID:8299728 Discrete localization of different DNA topoisomerases in HeLa and K562 cell nuclei and subnuclear fractions. PMID:9049244 Cell cycle-coupled relocation of types I and II topoisomerases and modulation of catalytic enzyme activities. |
| GO:0005730 nucleolus | IDA NOT PMID:9049244 Cell cycle-coupled relocation of types I and II topoisomeras... | ACCEPT | Summary: PMID:9049244 reports TOP2A is not localized inside nucleoli in A431 cells. Reason: The PMID:9049244 study reports extranucleolar/nucleoplasmic localization for TOP2A and excludes nucleolar localization in that context, which is captured as a NOT annotation in GOA. Other nucleolar annotations are supported by different PMIDs. Supporting Evidence: PMID:9049244 Cell cycle-coupled relocation of types I and II topoisomerases and modulation of catalytic enzyme activities. |
| GO:0005814 centriole | IDA PMID:9049244 Cell cycle-coupled relocation of types I and II topoisomeras... | ACCEPT | Summary: TOP2A detected at centrioles. Reason: Demonstrated in PMID:9049244 during cell cycle progression. This is a minor localization compared to chromosomal localization but has been observed. Supporting Evidence: PMID:9049244 Cell cycle-coupled relocation of types I and II topoisomerases and modulation of catalytic enzyme activities. |
| GO:0007059 chromosome segregation | IMP PMID:15965487 BRCA1 participates in DNA decatenation. | ACCEPT | Summary: TOP2A is essential for chromosome segregation in mitosis. Reason: Core function demonstrated in multiple studies (PMID:11136718, PMID:15456904, PMID:15965487). TOP2A decatenates sister chromatids allowing them to separate during anaphase. The deep research emphasizes this is 'absolutely required' and 'essential for cell viability' in dividing cells. Supporting Evidence: file:human/TOP2A/TOP2A-deep-research-openai.md During prophase and metaphase, Topo IIΞ± localizes to chromosome axes and centromeric regions, where it resolves the last DNA catenanes holding sister chromatids together. Experimental depletion or inhibition of TOP2A prior to mitosis causes severe defects: chromosomes fail to achieve proper compaction and remain connected by DNA strands, leading to anaphase bridges or chromosome breakage file:human/TOP2A/TOP2A-deep-research-falcon.md TOP2A is tightly linked to late cell-cycle stages and mitotic progression: it is needed to remove persistent sister-chromatid entanglements to enable faithful chromosome segregation. Its activity is integrated with the **decatenation checkpoint**, and cellular outcomes after TOP2A inhibition depend on genetic context such as **p53 status**. PMID:11136718 2001 Jan 2. Deacetylase activity associates with topoisomerase II and is necessary for etoposide-induced apoptosis. PMID:15456904 2004 Sep 29. Construction, characterization, and complementation of a conditional-lethal DNA topoisomerase IIalpha mutant human cell line. PMID:15965487 Jun 19. BRCA1 participates in DNA decatenation. |
| GO:0043130 ubiquitin binding | IMP PMID:15965487 BRCA1 participates in DNA decatenation. | ACCEPT | Summary: TOP2A binds ubiquitin. Reason: Demonstrated in PMID:15965487 in the context of BRCA1-mediated decatenation. This may be relevant for regulation or protein-protein interactions. Supporting Evidence: PMID:15965487 Jun 19. BRCA1 participates in DNA decatenation. |
| GO:0006974 DNA damage response | IDA PMID:16611985 Protein kinase C delta activates topoisomerase IIalpha to in... | ACCEPT | Summary: TOP2A participates in DNA damage response signaling. Reason: Demonstrated in PMID:16611985 showing TOP2A activation in response to DNA damage via PKC delta signaling. TOP2A's DNA cleavage activity can also trigger DNA damage checkpoints when the enzyme is inhibited by drugs. Supporting Evidence: PMID:16611985 Protein kinase C delta activates topoisomerase IIΞ± to induce apoptotic cell death in response to DNA damage |
| GO:0043065 positive regulation of apoptotic process | IDA PMID:16611985 Protein kinase C delta activates topoisomerase IIalpha to in... | ACCEPT | Summary: TOP2A activation can promote apoptosis. Reason: Demonstrated in PMID:16611985 in the context of DNA damage response. When activated by PKC delta, TOP2A activity contributes to apoptotic cell death. This is a context-dependent function. Supporting Evidence: PMID:16611985 Protein kinase C delta activates topoisomerase IIalpha to induce apoptotic cell death in response to DNA damage. |
Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)