dc.creator | Meir, Michal | es |
dc.creator | Galanty, Yaron | es |
dc.creator | Fernández Ávila, María Jesús | es |
dc.creator | Cruz García, Andrés | es |
dc.creator | Huertas Sánchez, Pablo | es |
dc.date.accessioned | 2017-03-17T11:12:41Z | |
dc.date.available | 2017-03-17T11:12:41Z | |
dc.date.issued | 2015 | |
dc.identifier.citation | Meir, M., Galanty, Y., Fernández Ávila, M.J., Cruz García, A. y Huertas Sánchez, P. (2015). The COP9 signalosome is vital for timely repair of DNA double-strand breaks. Nucleic Acids Research, 43 (9), 4517-4530. | |
dc.identifier.issn | 0305-1048 | es |
dc.identifier.uri | http://hdl.handle.net/11441/55956 | |
dc.description.abstract | The DNA damage response is vigorously activated by DNA double-strand breaks (DSBs). The chief mobilizer of the DSB response is the ATM protein kinase. We discovered that the COP9 signalosome (CSN) is a crucial player in the DSB response and an ATM target. CSN is a protein complex that regulates the activity of cullin ring ubiquitin ligase (CRL) complexes by removing the ubiquitin-like protein, NEDD8, from their cullin scaffold. We find that the CSN is physically recruited to DSB sites in a neddylation-dependent manner, and is required for timely repair of DSBs, affecting the balance between the two major DSB repair pathways—nonhomologous end-joining and homologous recombination repair (HRR). The CSN is essential for the processivity of deep end-resection—the initial step in HRR. Cullin 4a (CUL4A) is recruited to DSB sites in a CSN- and neddylation-dependent manner, suggesting that CSN partners with CRL4 in this pathway. Furthermore, we found that ATM-mediated phosphorylation of CSN subunit 3 on S410 is critical for proper DSB repair, and that loss of this phosphorylation site alone is sufficient to cause a DDR deficiency phenotype in the mouse. This novel branch of the DSB response thus significantly affects genome stability. | es |
dc.description.sponsorship | España Ministerio de Economía y Competitividad SAF2013-43255-P | es |
dc.format | application/pdf | es |
dc.language.iso | eng | es |
dc.publisher | Oxford University Press | es |
dc.relation.ispartof | Nucleic Acids Research, 43 (9), 4517-4530. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.title | The COP9 signalosome is vital for timely repair of DNA double-strand breaks | es |
dc.type | info:eu-repo/semantics/article | es |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Genética | es |
dc.relation.projectID | info:eu-repo/grantAgreement/MINECO/SAF2013-43255-P | es |
dc.relation.publisherversion | http://dx.doi.org/10.1093/nar/gkv270 | es |
dc.identifier.doi | 10.1093/nar/gkv270 | es |
idus.format.extent | 13 p. | es |
dc.journaltitle | Nucleic Acids Research | es |
dc.publication.volumen | 43 | es |
dc.publication.issue | 9 | es |
dc.publication.initialPage | 4517 | es |
dc.publication.endPage | 4530 | es |
dc.contributor.funder | Ministerio de Economía y Competitividad (MINECO). España | |