DNA topoisomerases I and II are nuclear enzymes; type II consists of two highly homologous isoforms: topoisomerase IIα and IIβ. This nuclear enzyme is involved in processes such as chromosome condensation, chromatid separation, and the relief of torsional stress that occurs during DNA transcription and replication. It catalyzes the transient breaking and rejoining of two strands of duplex DNA which allows the strands to pass through one another, thus altering the topology of DNA. Topoisomerases are very susceptible to various stresses. Acidic pH or oxidative stress can convert topoisomerases to DNA-breaking nucleases, causing genomic instability and cell death. DNA-damaging topoisomerase targeting drugs (e.g., etoposide) also convert topoisomerases to nucleases, with the enzyme usually trapped as an intermediate that is covalently bound to the 5+ end of the cleaved DNA strand(s).
Background References
1. "Identification of functional nuclear export sequences in human topoisomerase IIalpha and beta." Mirski S.E., Bielawski J.C., Cole S.P. Biochem. Biophys. Res. Commun. 306:905-911(2003)
2. "RECQL5 cooperates with Topoisomerase II alpha in DNA decatenation and cell cycle progression." Ramamoorthy M., Tadokoro T., Rybanska I., Ghosh A.K., Wersto R., May A., Kulikowicz T., Sykora P., Croteau D.L., Bohr V.A. Nucleic Acids Res. 40:1621-1635(2012)
Sequence Similarity
Belongs to the type II topoisomerase family.
Post-translational Modification
Phosphorylation has no effect on catalytic activity (By similarity). However, phosphorylation at Ser-1105 by CSNK1D/CK1 promotes DNA cleavable complex formation (By similarity).
ICC staining TOP2A in A431 cells (green). Cells were fixed in paraformaldehyde, permeabilised with 0.25% Triton X100/PBS and counterstained with DAPI in order to highlight the nucleus (blue).
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