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, Andres
A1 Butler, Logan R
A1 Williams, Jason G
A1 Muñoz-Cabello, Ana M
A1 Mueller, Geoffrey A
A1 London, Robert E
A1 Cortes-Ledesma, Felipe
A1 Williams, R Scott
K1 TOP2 cleavage complex resolution
K1 SUMOylation in DNA repair
K1 ZATT-TDP2 signaling axis
K1 Non-proteasomal DNA-protein crosslink repair
K1 SUMO2 engagement platform
K1 Anticancer drug-induced genotoxicity
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.
PB American Association for the Advancement of Science (AAAS)
YR 2017
FD 2017-09-29
LK http://hdl.handle.net/10668/11582
UL http://hdl.handle.net/10668/11582
LA en
NO Schellenberg MJ, Lieberman JA, Herrero-Ruiz A, Butler LR, Williams JG, Muñoz-Cabello AM, et al. ZATT (ZNF451)-mediated resolution of topoisomerase 2 DNA-protein cross-links. Science. 2017 Sep 29;357(6358):1412-1416.
DS RISalud
RD Oct 20, 2025