Gene Ontology annotation through association of InterPro records with GO terms.
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity.
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt.
Gene Ontology annotation based on curation of immunofluorescence data
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara.
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods.
Using a biochemical approach to identify the primary dimerization regions in human DNA topoisomerase IIalpha.
Human topoisomerase IIalpha and IIbeta interact with the C-terminal region of p53.
Modulation of human DNA topoisomerase IIalpha function by interaction with 14-3-3epsilon.
DNA topoisomerase IIalpha interacts with CAD nuclease and is involved in chromatin condensation during apoptotic execution.
Histone deacetylase interacts directly with DNA topoisomerase II.
Deacetylase activity associates with topoisomerase II and is necessary for etoposide-induced apoptosis.
The ATP-operated clamp of human DNA topoisomerase IIalpha: hyperstimulation of ATPase by "piggy-back" binding.
RNA helicase A interacts with dsDNA and topoisomerase IIalpha.
Construction, characterization, and complementation of a conditional-lethal DNA topoisomerase IIalpha mutant human cell line.
DNA ligation catalyzed by human topoisomerase II alpha.
BRCA1 participates in DNA decatenation.
Protein kinase C delta activates topoisomerase IIalpha to induce apoptotic cell death in response to DNA damage.
A study of the topoisomerase II activity in HIV-1 replication using the ferrocene derivatives as probes.
Nuclear interactions of topoisomerase II alpha and beta with phospholipid scramblase 1.
Functional interaction of DNA topoisomerase IIalpha with the beta-catenin and T-cell factor-4 complex.
The SET and transposase domain protein Metnase enhances chromosome decatenation: regulation by automethylation.
Metnase mediates resistance to topoisomerase II inhibitors in breast cancer cells.
Metnase promotes restart and repair of stalled and collapsed replication forks.
DNA cleavage and opening reactions of human topoisomerase IIα are regulated via Mg2+-mediated dynamic bending of gate-DNA.
The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts.
Taperin (c9orf75), a mutated gene in nonsyndromic deafness, encodes a vertebrate specific, nuclear localized protein phosphatase one alpha (PP1α) docking protein.
GANP regulates recruitment of AID to immunoglobulin variable regions by modulating transcription and nucleosome occupancy.
BAF complexes facilitate decatenation of DNA by topoisomerase IIα.
Identification of Novel Proteins Co-Purifying with Cockayne Syndrome Group B (CSB) Reveals Potential Roles for CSB in RNA Metabolism and Chromatin Dynamics.
The human RNA polymerase I structure reveals an HMG-like docking domain specific to metazoans.
Discrete localization of different DNA topoisomerases in HeLa and K562 cell nuclei and subnuclear fractions.
Cell cycle-coupled relocation of types I and II topoisomerases and modulation of catalytic enzyme activities.
The distribution and expression of the two isoforms of DNA topoisomerase II in normal and neoplastic human tissues.
SUMOylation of TOP2A with SUMO1
PIAS4 SUMOylates TOP2A with SUMO2,3
TOP2A gene gene expression is repressed by the DREAM complex
Falcon deep research report on TOP2A
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TOP2A (DNA topoisomerase IIα, EC 5.6.2.2) is a type IIA topoisomerase that
functions as a homodimeric, ATP-dependent nuclear enzyme resolving DNA
topological problems during replication and mitosis.
"The UniProt accession **P11388** corresponds to **human DNA topoisomerase 2-alpha (TOP2A; DNA topoisomerase IIα; EC 5.6.2.2)**, a **type IIA topoisomerase** that functions as a **homodimeric, ATP-dependent nuclear enzyme** involved in resolving DNA topological problems during replication and mitosis."
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The core catalytic reaction is an ATP-dependent duplex DNA strand-passage:
TOP2A binds a gate (G) segment, cleaves both strands, passes a transported (T)
duplex through the break, then reseals the G-segment.
"TOP2A catalyzes an **ATP-dependent duplex DNA strand-passage reaction**. Mechanistically, it binds a “gate” DNA segment (G-segment), cleaves both strands, transports a second duplex (T-segment) through the break, and then reseals the G-segment."
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A catalytic tyrosine forms a covalent 5'-phosphotyrosyl TOP2A-DNA intermediate
(reversible cleavage complex), and the cycle requires ATP and Mg2+.
"A catalytic **tyrosine** performs a nucleophilic attack on the DNA phosphodiester backbone to form a **covalent 5′-phosphotyrosyl TOP2A–DNA intermediate** (a reversible cleavage complex) that protects the DNA ends during the cycle."
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TOP2A substrate specificity is functional/structural rather than sequence-based:
it acts on DNA catenanes (decatenation of interlinked sister chromatids) and
positive/negative supercoils.
"TOP2A does not recognize a narrow DNA sequence substrate in the way many enzymes recognize small molecules. Its “specificity” is functional/structural: it targets **topological DNA substrates**, including:
- **DNA catenanes** (interlinked sister chromatids) requiring **decatenation** during mitosis.
- **Positive and negative supercoils**"
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TOP2A is nuclear and strongly associates with mitotic chromosome axes/scaffold;
a systematic analysis found no evidence for TOP2 localization to mitochondria.
"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**."
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TOP2A expression and abundance peak around G2/M with strong mitotic chromosome
association, matching its role in chromosome condensation and segregation.
"TOP2A is particularly critical in **proliferating cells**, with expression and abundance peaking around **G2/M**, and with strong **mitotic chromosome association**, matching its primary cellular role in supporting chromosome condensation and segregation."
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The isoform-specific C-terminal domain (CTD) provides nuclear localization and
chromatin-tethering functions and is modulated by diverse post-translational
modifications.
"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."
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TOP2A activity is integrated with the decatenation checkpoint, with cellular
outcomes after inhibition dependent on genetic context such as p53 status.
"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**."
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Clinically used TOP2-targeting chemotherapies (etoposide, doxorubicin/adriamycin,
amsacrine) are 'poisons' that stabilize the transient cleavage complex, converting
it into persistent DNA damage; catalytic inhibitors instead block ATPase/cycle
progression without stabilizing covalent complexes.
"many clinically used TOP2-targeting chemotherapies are **“poisons”** that stabilize the normally transient TOP2 cleavage complex, converting a controlled intermediate into persistent DNA damage that triggers cell-cycle arrest and cell death."
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TOP2A is a proliferation-associated cancer biomarker; amplification occurs in
~4% of ~24,000 solid tumors and can co-amplify with HER2, and TOP2A promotes
NSCLC migration/invasion/EMT via Wnt/β-catenin signaling.
"In **NSCLC**, TOP2A upregulation promoted migration, invasion, EMT, and survival; knockdown reduced these phenotypes, with effects tied to **Wnt/β-catenin/Wnt3a** signaling."