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DC Field | Value | Language |
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dc.contributor.author | Martrat Sànchez, Griselda | - |
dc.contributor.author | Maxwell, Christopher A. | - |
dc.contributor.author | Porta de la Riva, Montserrat | - |
dc.contributor.author | Bonifaci Cano, Núria | - |
dc.contributor.author | Gómez Baldó, Laia | - |
dc.contributor.author | Lázaro García, Conxi | - |
dc.contributor.author | Blanco Guillermo, Ignacio | - |
dc.contributor.author | Aguilar, Helena | - |
dc.contributor.author | Fernández Rodríguez, Juana | - |
dc.contributor.author | Cuadras, Daniel | - |
dc.contributor.author | Moreno Aguado, Víctor | - |
dc.contributor.author | Cerón Madrigal, Julián | - |
dc.contributor.author | Pujana Genestar, M. Ángel | - |
dc.date.accessioned | 2018-09-03T14:04:58Z | - |
dc.date.available | 2018-09-03T14:04:58Z | - |
dc.date.issued | 2011-04-05 | - |
dc.identifier.issn | 1465-542X | - |
dc.identifier.uri | http://hdl.handle.net/2445/124234 | - |
dc.description.abstract | Introduction: Proteins encoded by Fanconi anemia (FA) and/or breast cancer (BrCa) susceptibility genes cooperate in a common DNA damage repair signaling pathway. To gain deeper insight into this pathway and its influence on cancer risk, we searched for novel components through protein physical interaction screens. Methods: Protein physical interactions were screened using the yeast two-hybrid system. Co-affinity purifications and endogenous co-immunoprecipitation assays were performed to corroborate interactions. Biochemical and functional assays in human, mouse and Caenorhabditis elegans models were carried out to characterize pathway components. Thirteen FANCD2-monoubiquitinylation-positive FA cell lines excluded for genetic defects in the downstream pathway components and 300 familial BrCa patients negative for BRCA1/2 mutations were analyzed for genetic mutations. Common genetic variants were genotyped in 9,573 BRCA1/2 mutation carriers for associations with BrCa risk. Results: A previously identified co-purifying protein with PALB2 was identified, MRG15 (MORF4L1 gene). Results in human, mouse and C. elegans models delineate molecular and functional relationships with BRCA2, PALB2, RAD51 and RPA1 that suggest a role for MRG15 in the repair of DNA double-strand breaks. Mrg15-deficient murine embryonic fibroblasts showed moderate sensitivity to g-irradiation relative to controls and reduced formation of Rad51 nuclear foci. Examination of mutants of MRG15 and BRCA2 C. elegans orthologs revealed phenocopy by accumulation of RPA-1 (human RPA1) nuclear foci and aberrant chromosomal compactions in meiotic cells. However, no alterations or mutations were identified for MRG15/MORF4L1 in unclassified FA patients and BrCa familial cases. Finally, no significant associations between common MORF4L1 variants and BrCa risk for BRCA1 or BRCA2 mutation carriers were identified: rs7164529, Ptrend = 0.45 and 0.05, P2df = 0.51 and 0.14, respectively; and rs10519219, Ptrend = 0.92 and 0.72, P2df = 0.76 and 0.07, respectively. Conclusions: While the present study expands on the role of MRG15 in the control of genomic stability, weak associations cannot be ruled out for potential low-penetrance variants at MORF4L1 and BrCa risk among BRCA2 mutation carriers. | - |
dc.format.extent | 14 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | BioMed Central | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1186/bcr2862 | - |
dc.relation.ispartof | Breast Cancer Research, 2011, vol. 13, num. R40 | - |
dc.relation.uri | https://doi.org/10.1186/bcr2862 | - |
dc.rights | cc-by (c) Martrat, Griselda et al., 2011 | - |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es | - |
dc.source | Articles publicats en revistes (Ciències Clíniques) | - |
dc.subject.classification | Càncer de mama | - |
dc.subject.classification | Anèmia aplàstica | - |
dc.subject.other | Breast cancer | - |
dc.subject.other | Aplastic anemia | - |
dc.title | Exploring the link between MORF4L1 and risk of breast cancer | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 595975 | - |
dc.date.updated | 2018-09-03T14:04:59Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 21124932 | - |
dc.identifier.pmid | 21466675 | - |
Appears in Collections: | Articles publicats en revistes (Ciències Clíniques) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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595975.pdf | 2.01 MB | Adobe PDF | View/Open |
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