Please use this identifier to cite or link to this item:
Title: ZATT (ZNF451)-mediated resolution of topoisomerase 2 DNA-protein cross-links.
Authors: Schellenberg, Matthew J
Lieberman, Jenna Ariel
Herrero-Ruiz, Andrés
Butler, Logan R
Williams, Jason G
Muñoz-Cabello, Ana M
Mueller, Geoffrey A
London, Robert E
Cortés-Ledesma, Felipe
Williams, R Scott
metadata.dc.subject.mesh: Aminoacyltransferases
Bacterial Proteins
Catalytic Domain
DNA Damage
DNA Repair
DNA Topoisomerases, Type II
DNA-Binding Proteins
Gene Knockdown Techniques
HEK293 Cells
Luminescent Proteins
Nuclear Proteins
Phosphoric Diester Hydrolases
Recombinant Proteins
Saccharomyces cerevisiae Proteins
Small Ubiquitin-Related Modifier Proteins
Topoisomerase II Inhibitors
Transcription Factors
Ubiquitin-Protein Ligases
Issue Date: 14-Sep-2017
Abstract: 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.
metadata.dc.identifier.doi: 10.1126/science.aam6468
Appears in Collections:Producción 2020

Files in This Item:
There are no files associated with this item.

This item is protected by original copyright

Except where otherwise noted, Items on the Andalusian Health Repository site are licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives License.