TOP2A

TOP2A Full Name

topoisomerase (DNA) II alpha 170kDa

TOP2A Introduction

DNA topoisomerase II alpha (TOP2A) is a 170 kDa nuclear metalloenzyme that plays an indispensable role in managing DNA topology during essential cellular processes. As a cell cycle-dependent enzyme, TOP2A expression peaks during the G2 and M phases. It functions by creating transient, ATP-dependent double-strand breaks in the DNA backbone, allowing another intact DNA double helix to pass through the transient gate before seamlessly resealing the break. This unique catalytic strand-passage mechanism is absolutely critical for relieving torsional stress during DNA replication and transcription, as well as for resolving intertwined DNA molecules to ensure proper chromosome condensation and sister chromatid segregation during cell division.

Figure 1. The interaction of type IIA topoisomerases with DNA. (Source: Hardin AH, et al. 2011)

Because TOP2A is a fundamental engine of cell proliferation, its dysregulation is heavily implicated in human oncogenesis. Clinically, the TOP2A gene, located on chromosome 17q21.2 in close proximity to the HER2 oncogene, is frequently co-amplified or overexpressed in a variety of aggressive malignancies, including breast cancer, non-small cell lung cancer, and ovarian carcinoma. In these contexts, elevated TOP2A levels serve as a robust biomarker for high tumor proliferation and poor patient prognosis. More importantly, TOP2A is the primary molecular target for several widely utilized classes of antineoplastic agents, such as anthracyclines (e.g., doxorubicin) and epipodophyllotoxins (e.g., etoposide). These drugs act as "topoisomerase poisons" by stabilizing the transient TOP2A-DNA cleavage complex, thereby accumulating lethal double-strand DNA breaks that ultimately trigger cancer cell apoptosis.

Alternate Names for TOP2A

TOP2A; Topo IIA; topoisomerase (DNA) II alpha 170kDa; TOP2; TP2A; DNA topoisomerase 2-alpha; DNA gyrase; DNA topoisomerase II, 170 kD; DNA topoisomerase (ATP-hydrolyzing); DNA topoisomerase II, alpha isozyme;

• 1. Hardin AH, et al. Direct measurement of DNA bending by type IIA topoisomerases: implications for non-equilibrium topology simplification. Nucleic Acids Res. 2011 Jul;39(13):5729-43.
  2. Nitiss JL. Targeting DNA topoisomerase II in cancer chemotherapy. Nat Rev Cancer. 2009 May;9(5):338-50.