Publication:
ZATT (ZNF451)-mediated resolution of topoisomerase 2 DNA-protein cross-links.

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dc.contributor.authorSchellenberg, Matthew J
dc.contributor.authorLieberman, Jenna Ariel
dc.contributor.authorHerrero-Ruiz, Andrés
dc.contributor.authorButler, Logan R
dc.contributor.authorWilliams, Jason G
dc.contributor.authorMuñoz-Cabello, Ana M
dc.contributor.authorMueller, Geoffrey A
dc.contributor.authorLondon, Robert E
dc.contributor.authorCortés-Ledesma, Felipe
dc.contributor.authorWilliams, R Scott
dc.date.accessioned2023-01-25T09:52:10Z
dc.date.available2023-01-25T09:52:10Z
dc.date.issued2017-09-14
dc.description.abstractTopoisomerase 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.
dc.identifier.doi10.1126/science.aam6468
dc.identifier.essn1095-9203
dc.identifier.pmcPMC5623066
dc.identifier.pmid28912134
dc.identifier.pubmedURLhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5623066/pdf
dc.identifier.unpaywallURLhttps://europepmc.org/articles/pmc5623066?pdf=render
dc.identifier.urihttp://hdl.handle.net/10668/11582
dc.issue.number6358
dc.journal.titleScience (New York, N.Y.)
dc.journal.titleabbreviationScience
dc.language.isoen
dc.organizationCentro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER
dc.organizationInstituto de Biomedicina de Sevilla-IBIS
dc.organizationHospital Universitario Virgen del Rocío
dc.page.number1412-1416
dc.pubmedtypeJournal Article
dc.pubmedtypeResearch Support, N.I.H., Extramural
dc.pubmedtypeResearch Support, N.I.H., Intramural
dc.pubmedtypeResearch Support, Non-U.S. Gov't
dc.pubmedtypeResearch Support, U.S. Gov't, Non-P.H.S.
dc.rights.accessRightsopen access
dc.subject.meshAminoacyltransferases
dc.subject.meshAnimals
dc.subject.meshBacterial Proteins
dc.subject.meshBiocatalysis
dc.subject.meshCatalytic Domain
dc.subject.meshDNA
dc.subject.meshDNA Damage
dc.subject.meshDNA Repair
dc.subject.meshDNA Topoisomerases, Type II
dc.subject.meshDNA-Binding Proteins
dc.subject.meshEtoposide
dc.subject.meshGene Knockdown Techniques
dc.subject.meshHEK293 Cells
dc.subject.meshHumans
dc.subject.meshImmunoprecipitation
dc.subject.meshLuminescent Proteins
dc.subject.meshMice
dc.subject.meshNuclear Proteins
dc.subject.meshPhosphoric Diester Hydrolases
dc.subject.meshRecombinant Proteins
dc.subject.meshSaccharomyces cerevisiae Proteins
dc.subject.meshSmall Ubiquitin-Related Modifier Proteins
dc.subject.meshSumoylation
dc.subject.meshTopoisomerase II Inhibitors
dc.subject.meshTranscription Factors
dc.subject.meshUbiquitin-Protein Ligases
dc.titleZATT (ZNF451)-mediated resolution of topoisomerase 2 DNA-protein cross-links.
dc.typeresearch article
dc.type.hasVersionAM
dc.volume.number357
dspace.entity.typePublication

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Centro Andaluz de Biología Molecular (CABIMER)
Instituto de Investigación Biomédica de Sevilla (IBIS)
SAS - Hospital Universitario Virgen del Rocío

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