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http://hdl.handle.net/10668/11582| 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 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 |
| 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. |
| URI: | http://hdl.handle.net/10668/11582 |
| metadata.dc.identifier.doi: | 10.1126/science.aam6468 |
| Appears in Collections: | Producción 2020 |
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