DNA-topoisomerase II cleavage complex (TOP2cc) (TOP2cc)

The DNA-topoisomerase II cleavage complex (TOP2cc) is a transient intermediate formed during the catalytic cycle of topoisomerase II enzymes, which are essential for managing DNA topology during replication, transcription, and chromosome segregation (Nitiss, 2009, Nature Reviews Cancer [1]). In this state, the enzyme creates a double-strand break and becomes covalently linked to the 5' ends of the DNA via a phosphotyrosyl bond (Pommier et al., 2016, Chemistry & Biology [2]). While this complex is normally short-lived, it is the primary target for a class of chemotherapy drugs known as topoisomerase II poisons (Deweese & Osheroff, 2009, Nucleic Acids Research [3]). These drugs, including etoposide and doxorubicin, stabilize the TOP2cc, preventing the religation of the DNA strands (StatPearls, 2023 [4]). The resulting accumulation of stabilized cleavage complexes leads to permanent DNA double-strand breaks, which trigger apoptosis in rapidly dividing cancer cells (Nitiss, 2009 [1]). However, the formation of these complexes can also lead to genomic instability and secondary malignancies, such as treatment-related leukemia, particularly when the TOP2B isoform is involved in non-dividing cells (Pommier et al., 2016 [2]).

Other names

DNA at topoisomerase II cleavage sitesTOP2-DNA covalent complexTopoisomerase II-DNA complexTOP2 cleavage complexDNA-topoisomerase II covalent complex

Stabilization of the covalent DNA-topoisomerase II intermediate (cleavage complex), preventing DNA religation and inducing permanent double-strand breaks (Nitiss, 2009 [1]; Pommier et al., 2016 [2]).