Publication: ZATT (ZNF451)-mediated resolution of topoisomerase 2 DNA-protein cross-links.
No Thumbnail Available
Identifiers
Date
2017-09-29
Authors
Schellenberg, Matthew J
Lieberman, Jenna Ariel
Herrero-Ruiz, Andres
Butler, Logan R
Williams, Jason G
Muñoz-Cabello, Ana M
Mueller, Geoffrey A
London, Robert E
Cortes-Ledesma, Felipe
Williams, R Scott
Advisors
Journal Title
Journal ISSN
Volume Title
Publisher
American Association for the Advancement of Science (AAAS)
Metrics
Export
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.
Description
MeSH Terms
Aminoacyltransferases
Animals
Bacterial Proteins
Biocatalysis
Catalytic Domain
DNA
DNA Damage
DNA Repair
DNA Topoisomerases, Type II
DNA-Binding Proteins
Etoposide
Gene Knockdown Techniques
HEK293 Cells
Humans
Immunoprecipitation
Luminescent Proteins
Mice
Nuclear Proteins
Phosphoric Diester Hydrolases
Recombinant Proteins
Saccharomyces cerevisiae Proteins
Small Ubiquitin-Related Modifier Proteins
Sumoylation
Topoisomerase II Inhibitors
Transcription Factors
Ubiquitin-Protein Ligases
Animals
Bacterial Proteins
Biocatalysis
Catalytic Domain
DNA
DNA Damage
DNA Repair
DNA Topoisomerases, Type II
DNA-Binding Proteins
Etoposide
Gene Knockdown Techniques
HEK293 Cells
Humans
Immunoprecipitation
Luminescent Proteins
Mice
Nuclear Proteins
Phosphoric Diester Hydrolases
Recombinant Proteins
Saccharomyces cerevisiae Proteins
Small Ubiquitin-Related Modifier Proteins
Sumoylation
Topoisomerase II Inhibitors
Transcription Factors
Ubiquitin-Protein Ligases
DeCS Terms
Topoisomerasas del ADN tipo II
Daño al ADN
Reparación del ADN
Ligasas de proteínas ubiquitina
Proteína SUMO-1
Proteólisis
Fosfodiesterasa de ADN tirosil
Daño al ADN
Reparación del ADN
Ligasas de proteínas ubiquitina
Proteína SUMO-1
Proteólisis
Fosfodiesterasa de ADN tirosil
CIE Terms
Keywords
TOP2 cleavage complex resolution, SUMOylation in DNA repair, ZATT-TDP2 signaling axis, Non-proteasomal DNA-protein crosslink repair, SUMO2 engagement platform, Anticancer drug-induced genotoxicity
Citation
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.