Figure 1.
A pathway for repairing topoisomerase II–mediated DNA damage.
Topoisomerase II, a homodimeric protein, cleaves both strands of DNA, and generates a four base overhang. In the absence of perturbation (such as topoisomerase poisons), religation of the broken strands is kinetically favored, and is likely inhibited by topoisomerase poisons. Recognition of the trapped protein may trigger modification and proteolysis, leaving a short peptide covalently bound to DNA. This peptide can be removed by Tdp2 cleavage of the tyrosyl phosphate bond, leaving DNA with a double-strand break. If the broken DNA is not processed prior to ligation, e.g., by DNA ligase IV in the NHEJ pathway, the result will be error-free repair of the trapped covalent complex.