Abstract
Recently, ZATT (also known as ZNF451 or Zpf451) was reported by Schellenberg et al. to aid the removal of Topoisomerase II cleavage complexes by stimulating the phosphodiesterase activity of Tyrosyl DNA Phosphodiesterase 2. Although the full implication of this discovery is unknown, it will help us understand how cells respond to topoisomerase-induced genome damage and chemotherapeutic topoisomerase 'poisons'.
Highlights
The enzyme 5′-tyrosyl DNA phosphodiesterase 2 (TDP2) can initiate the repair of TOP2cc by hydrolytic removal of trapped topoisomerase peptide from the 5′-termini of DSBs, thereby allowing the DSB to be religated [3]
The authors show that TDP2 interacts with ZNF451, a SUMO E3/E4 ligase/elongase that they denote ZATT (Zinc finger protein Associated with TDP2 and TOP2)
ZNF451/ ZATT employs tandem sumo interacting motifs (SIMs) and a C2H2 zinc finger to promote SUMO2 conjugation and chain elongation in vitro, both in unperturbed cells and in perturbed cells treated with topoisomerase I poison, camptothecin [8]
Summary
The enzyme 5′-tyrosyl DNA phosphodiesterase 2 (TDP2) can initiate the repair of TOP2cc by hydrolytic removal of trapped topoisomerase peptide from the 5′-termini of DSBs, thereby allowing the DSB to be religated [3]. Schellenberg et al.[7] challenge this model and clarify how TDP2 processes TOP2cc. In contrast to previous models, Schellenberg et al [7] identify a new TDP2dependent DNA repair pathway that involves TOP2 sumoylation independent of ubiquitination and proteasome activity.
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