dc.creator | Alonso de la Vega, Ignacio | es |
dc.creator | Paz Cabrera, María Cristina | es |
dc.creator | Rother, Magdalena B | es |
dc.creator | Wiegant, Wouter W | es |
dc.creator | Checa Rodríguez, Cintia | es |
dc.creator | Hernández Fernaud, Juan Ramón | es |
dc.creator | Huertas Sánchez, Pablo | es |
dc.creator | Freire, Raimundo | es |
dc.creator | Attikum, Haico van | es |
dc.creator | Smits, Veronique A J | es |
dc.date.accessioned | 2020-04-21T10:41:59Z | |
dc.date.available | 2020-04-21T10:41:59Z | |
dc.date.issued | 2020 | |
dc.identifier.citation | Alonso de la Vega, I., Paz Cabrera, M.C., Rother, M.B., Wiegant, W.W., Checa Rodríguez, C., Hernández Fernaud, J.R.,...,Smits, .A.J. (2020). PHF2 regulates homology-directed DNA repair by controlling the resection of DNA double strand breaks. Nucleic Acids Research, 48 (9), 4915-4927. | |
dc.identifier.issn | 1362-4962 | es |
dc.identifier.uri | https://hdl.handle.net/11441/95531 | |
dc.description.abstract | Post-translational histone modifications and chromatin remodelling play a critical role controlling the integrity of the genome. Here, we identify histone lysine demethylase PHF2 as a novel regulator of the DNA damage response by regulating DNA damage-induced focus formation of 53BP1 and BRCA1, critical factors in the pathway choice for DNA double strand break repair. PHF2 knockdown leads to impaired BRCA1 focus formation and delays the resolution of 53BP1 foci. Moreover, irradiation-induced RPA phosphorylation and focus formation, as well as localization of CtIP, required for DNA end resection, to sites of DNA lesions are affected by depletion of PHF2. These results are indicative of a defective resection of double strand breaks and thereby an impaired homologous recombination upon PHF2 depletion. In accordance with these data, Rad51 focus formation and homology-directed double strand break repair is inhibited in cells depleted for PHF2. Importantly, we demonstrate that PHF2 knockdown decreases CtIP and BRCA1 protein and mRNA levels, an effect that is dependent on the demethylase activity of PHF2. Furthermore, PHF2-depleted cells display genome instability and are mildly sensitive to the inhibition of PARP. Together these results demonstrate that PHF2 promotes DNA repair by homologous recombination by controlling CtIP-dependent resection of double strand breaks. | es |
dc.description.sponsorship | España Ministerio de Ciencia e Innovacion SAF2016-80626-R | es |
dc.description.sponsorship | España, Fundación Canaria Instituto de Investigación Sanitaria de Canarias (FIISC) [PIFUN16/18] | es |
dc.format | application/pdf | es |
dc.format.extent | 13 p. | es |
dc.language.iso | eng | es |
dc.publisher | Oxford University Press | es |
dc.relation.ispartof | Nucleic Acids Research, 48 (9), 4915-4927. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.title | PHF2 regulates homology-directed DNA repair by controlling the resection of DNA double strand breaks | 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.contributor.affiliation | Universidad de Sevilla. Departamento de Genética | es |
dc.relation.projectID | SAF2016-80626-R | es |
dc.relation.projectID | SAF2016-74855-P | es |
dc.relation.projectID | PIFUN16/18 | es |
dc.relation.publisherversion | http://dx.doi.org/10.1093/nar/gkaa196 | es |
dc.identifier.doi | 10.1093/nar/gkaa196 | es |
dc.contributor.group | Universidad de Sevilla. Metabolismo del DNA | es |
dc.journaltitle | Nucleic Acids Research | es |
dc.publication.volumen | 48 | |
dc.publication.issue | 9 | |
dc.publication.initialPage | 4915 | |
dc.publication.endPage | 4927 | |
dc.contributor.funder | Ministerio de Ciencia e Innovación (MICIN). España | es |
dc.contributor.funder | Fundación Canaria Instituto de Investigación Sanitaria de Canarias (FIISC), España | es |