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TDP2/TTRAP Is the Major 5′-Tyrosyl DNA Phosphodiesterase Activity in Vertebrate Cells and Is Critical for Cellular Resistance to Topoisomerase II-induced DNA Damage
dc.creator | Zeng, Zhihong | es |
dc.creator | Cortés Ledesma, Felipe | es |
dc.creator | El Khamisy, Sherif F. | es |
dc.creator | Caldecott, Keith W. | es |
dc.date.accessioned | 2017-09-19T13:46:56Z | |
dc.date.available | 2017-09-19T13:46:56Z | |
dc.date.issued | 2011 | |
dc.identifier.citation | Zeng, Z., Cortés Ledesma, F., El Khamisy, S.F. y Caldecott, .W. (2011). TDP2/TTRAP Is the Major 5′-Tyrosyl DNA Phosphodiesterase Activity in Vertebrate Cells and Is Critical for Cellular Resistance to Topoisomerase II-induced DNA Damage. Journal of Biological Chemistry, 286 (1), 403-409. | |
dc.identifier.issn | 0021-9258 | es |
dc.identifier.uri | http://hdl.handle.net/11441/64488 | |
dc.description.abstract | Topoisomerase II (Top2) activity involves an intermediate in which the topoisomerase is covalently bound to a DNA double-strand break via a 5′-phosphotyrosyl bond. Although these intermediates are normally transient, they can be stabilized by antitumor agents that act as Top2 “poisons,” resulting in the induction of cytotoxic double-strand breaks, and they are implicated in the formation of site-specific translocations that are commonly associated with cancer. Recently, we revealed that TRAF and TNF receptor-associated protein (TTRAP) is a 5′-tyrosyl DNA phosphodiesterase (5′-TDP) that can cleave 5′-phosphotyrosyl bonds, and we denoted this protein tyrosyl DNA phosphodiesterase-2 (TDP2). Here, we have generated TDP2-deleted DT40 cells, and we show that TDP2 is the major if not the only 5′-TDP activity present in vertebrate cells. We also show that TDP2-deleted DT40 cells are highly sensitive to the anticancer Top2 poison, etoposide, but are not hypersensitive to the Top1 poison camptothecin or the DNA-alkyating agent methyl methanesulfonate. These data identify an important mechanism for resistance to Top2-induced chromosome breakage and raise the possibility that TDP2 is a significant factor in cancer development and treatment. | es |
dc.format | application/pdf | es |
dc.language.iso | eng | es |
dc.publisher | American Society for Biochemistry and Molecular Biology | es |
dc.relation.ispartof | Journal of Biological Chemistry, 286 (1), 403-409. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | Cancer Therapy | es |
dc.subject | DNA Damage | es |
dc.subject | DNA Repair | es |
dc.subject | DNA Topoisomerase | es |
dc.subject | Phosphodiesterases | es |
dc.title | TDP2/TTRAP Is the Major 5′-Tyrosyl DNA Phosphodiesterase Activity in Vertebrate Cells and Is Critical for Cellular Resistance to Topoisomerase II-induced DNA Damage | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.relation.publisherversion | http://dx.doi.org/ 10.1074/jbc.M110.181016 | es |
dc.identifier.doi | 10.1074/jbc.M110.181016 | es |
idus.format.extent | 6 p. | es |
dc.journaltitle | Journal of Biological Chemistry | es |
dc.publication.volumen | 286 | es |
dc.publication.issue | 1 | es |
dc.publication.initialPage | 403 | es |
dc.publication.endPage | 409 | es |
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1pubmed.pdf | 2.088Mb | [PDF] | Ver/ | |