RT Journal Article
T1 ZATT (ZNF451)-mediated resolution of topoisomerase 2 DNA-protein cross-links.
A1 Schellenberg, Matthew J
A1 Lieberman, Jenna Ariel
A1 Herrero-Ruiz, Andrés
A1 Butler, Logan R
A1 Williams, Jason G
A1 Muñoz-Cabello, Ana M
A1 Mueller, Geoffrey A
A1 London, Robert E
A1 Cortés-Ledesma, Felipe
A1 Williams, R Scott
AB Topoisomerase 2 (TOP2) DNA transactions proceed via formation of the TOP2 cleavage complex (TOP2cc), a covalent enzyme-DNA reaction intermediate that is vulnerable to trapping by potent anticancer TOP2 drugs. How genotoxic TOP2 DNA-protein cross-links are resolved is unclear. We found that the SUMO (small ubiquitin-related modifier) ligase ZATT (ZNF451) is a multifunctional DNA repair factor that controls cellular responses to TOP2 damage. ZATT binding to TOP2cc facilitates a proteasome-independent tyrosyl-DNA phosphodiesterase 2 (TDP2) hydrolase activity on stalled TOP2cc. The ZATT SUMO ligase activity further promotes TDP2 interactions with SUMOylated TOP2, regulating efficient TDP2 recruitment through a "split-SIM" SUMO2 engagement platform. These findings uncover a ZATT-TDP2-catalyzed and SUMO2-modulated pathway for direct resolution of TOP2cc.
YR 2017
FD 2017-09-14
LK http://hdl.handle.net/10668/11582
UL http://hdl.handle.net/10668/11582
LA en
DS RISalud
RD Apr 10, 2025