TOP2A

DNA topoisomerase 2-alpha UniProt accession P11388

Key decatenating enzyme that alters DNA topology by binding to two double-stranded DNA molecules, generating a double-stranded break in one of the strands, passing the intact strand through the broken strand, and religating the broken strand (PubMed:17567603, PubMed:18790802, PubMed:22013166, PubMed:22323612, PubMed:27754753). May play a role in regulating the period length of BMAL1 transcriptional oscillation (By similarity)

Source: UniProt

Homodimer. Interacts with COPS5. Interacts with RECQL5; this stimulates DNA decatenation.

Interacts with SETMAR; stimulates the topoisomerase activity (PubMed:18790802, PubMed:20457750). Interacts with DHX9; this interaction occurs in a E2 enzyme UBE2I- and RNA-dependent manner, negatively regulates DHX9-mediated double-stranded DNA and RNA duplex helicase activity and stimulates TOP2A-mediated supercoiled DNA relaxation activity (PubMed:12711669). Interacts with HNRNPU (via C-terminus); this interaction protects the topoisomerase TOP2A from degradation and positively regulates the relaxation of supercoiled DNA in a RNA-dependent manner (By similarity).

Interacts with MCM3AP isoform GANP (PubMed:23652018). Interacts with ERCC6 (PubMed:26030138). Interacts with PLSCR1 (PubMed:17567603).

Interacts with GCNA; this interaction allows the resolution of topoisomerase II (TOP2A) DNA-protein cross-links (By similarity). Interacts with POL1RA/RPA1 (via dock II) and UBTF in the context of Pol I complex; may assist Pol I transcription initiation by releasing supercoils occurring during DNA unwinding. Interacts with TPRN; TPRN interacts with a number of DNA damage response proteins, is recruited to sites of DNA damage and may play a role in DNA damage repair (PubMed:23213405).

Interacts with FBXO28; this interaction leads to TOP2A proteasomal degradation (PubMed:27754753)

Source: UniProt
Cytoplasm, Nucleus, nucleoplasm, Nucleus, Nucleus, nucleolus
Source: UniProt

Expressed in the tonsil, spleen, lymph node, thymus, skin, pancreas, testis, colon, kidney, liver, brain and lung (PubMed:9155056). Also found in high-grade lymphomas, squamous cell lung tumors and seminomas (PubMed:9155056)

Source: UniProt

The N-terminus has several structural domains; the ATPase domain (about residues 1-265), the transducer domain (about 266-428) and the toprim domain (455-572) (PubMed:25202966). Comparing different structures shows ATP hydrolysis induces domain shifts in the N-terminus that are probably part of the mechanism of DNA cleavage and rejoining (PubMed:25202966)

Source: UniProt
  • Transcription of E2F targets under negative control by DREAM complex
  • SUMOylation of DNA replication proteins
Source: Reactome via UniProt

Mutations

No mutation information available.

Synthetic Lethal Network

Genes with an experimentally identified or computationally predicted synthetic-lethal relationship to TOP2A, aggregated across our SSL data sources. Click any partner node to view that gene’s page.

Nodes and edges are coloured by the SSL data source. Partners appearing in more than one source are shown in grey.

BioGRID SLOrth SynLethDB MexDrugs Multi-source
Sources: BioGRID, SLOrth, SynLethDB, MexDrugs

Clinical Trials

Total Trials Found: 6

NCT ID Condition Brief Title Phase Status
NCT02339532 Breast Cancer Neoadjuvant Phase II Trial in Patients With T1c Operable, HER2-positive Breast Cancer According to TOP2A Status PHASE2 COMPLETED
NCT04055753 Soft Tissue Sarcoma Study to Assess TOPO2A as a Biomarker for Sensitivity to Doxorubicin/Doxil in Soft Tissue Sarcoma N/A ACTIVE_NOT_RECRUITING
NCT00689156 Breast Neoplasms Epirubicin or Not in Patients With TOP2A (Topoisomerase (DNA) II Alpha (170kD)) Normal Early Breast Cancer PHASE3 COMPLETED
NCT03930680 Degradation of Top2b and Top2a in Human by Dexrazoxane, Time Course and Degradation of Top2b in Human by Dexrazoxane, Effects of Dexrazoxane on Healthy Human Prevention of Heart Failure Induced by Doxorubicin With Early Administration of Dexrazoxane PHASE1 COMPLETED
NCT00898898 Breast Cancer Studying Tissue Samples From Women With Breast Cancer Who Were Treated on Clinical Trial NCCTG-N9831 N/A COMPLETED
NCT00162812 Breast Cancer Topoisomerase II Alpha Gene Amplification and Protein Overexpression Predicting Efficacy of Epirubicin PHASE2 TERMINATED