dc.creator | Sastre Moreno, Guillermo | es |
dc.creator | Pryor, John M. | es |
dc.creator | Moreno Oñate, Marta | es |
dc.creator | Herrero Ruiz, Andrés M. | es |
dc.creator | Cortés Ledesma, Felipe | es |
dc.creator | Ruiz Pérez, José Francisco | es |
dc.date.accessioned | 2018-09-20T09:22:26Z | |
dc.date.available | 2018-09-20T09:22:26Z | |
dc.date.issued | 2018 | |
dc.identifier.citation | Sastre Moreno, G., Pryor, J.M., Moreno Oñate, M., Herrero Ruiz, A.M., Cortés Ledesma, F. y Ruiz Pérez, J.F. (2018). Regulation of human Polλ by ATM-mediated phosphorylation during Non-Homologous End Joining. DNA Repair, 51, 31-45. | |
dc.identifier.issn | 1568-7856 | es |
dc.identifier.uri | https://hdl.handle.net/11441/78670 | |
dc.description.abstract | DNA double strand breaks (DSBs) trigger a variety of cellular signaling processes, collectively termed the DNA-damage response (DDR), that are primarily regulated by protein kinase ataxia-telangiectasia mutated (ATM). Among DDR activated processes, the repair of DSBs by non-homologous end joining (NHEJ) is essential. The proper coordination of NHEJ factors is mainly achieved through phosphorylation by an ATM-related kinase, the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), although the molecular basis for this regulation has yet to be fully elucidated. In this study we identify the major NHEJ DNA polymerase, DNA polymerase lambda (Polλ), as a target for both ATM and DNA-PKcs in human cells. We show that Polλ is efficiently phosphorylated by DNA-PKcs in vitro and predominantly by ATM after DSB induction with ionizing radiation (IR) in vivo. We identify threonine 204 (T204) as a main target for ATM/DNA-PKcs phosphorylation on human Polλ, and establish that its phosphorylation may facilitate the repair of a subset of IR-induced DSBs and the efficient Polλ-mediated gap-filling during NHEJ. Molecular evidence suggests that Polλ phosphorylation might favor Polλ interaction with the DNA-PK complex at DSBs. Altogether, our work provides the first demonstration of how Polλ is regulated by phosphorylation to connect with the NHEJ core machinery during DSB repair in human cells. | es |
dc.description.sponsorship | España MINECO y la Comisión Europea (European Regional Development Fund) to J.F.R. RYC-2011-08752, BFU2013-44343-P) and to F.C-L. (SAF2014-55532-R). | es |
dc.format | application/pdf | es |
dc.language.iso | eng | es |
dc.publisher | Elsevier | es |
dc.relation.ispartof | DNA Repair, 51, 31-45. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.title | Regulation of human Polλ by ATM-mediated phosphorylation during Non-Homologous End Joining | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/acceptedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Bioquímica Vegetal y Biología Molecular | es |
dc.relation.projectID | RYC-2011-08752 | es |
dc.relation.projectID | BFU2013-44343-P | es |
dc.relation.projectID | SAF2014-55532-R | es |
dc.relation.publisherversion | http://dx.doi.org/10.1016/j.dnarep.2017.01.004 | es |
dc.identifier.doi | 10.1016/j.dnarep.2017.01.004 | es |
idus.format.extent | 15 p. | es |
dc.journaltitle | DNA Repair | es |
dc.publication.volumen | 51 | es |
dc.publication.initialPage | 31 | es |
dc.publication.endPage | 45 | es |
dc.contributor.funder | Ministerio de Economía y Competitividad (MINECO). España | |
dc.contributor.funder | European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER) | |