dc.contributor.author |
Martrat, Griselda |
dc.contributor.author |
Maxwell, Christopher A. |
dc.contributor.author |
Porta de la Riva, Montserrat |
dc.contributor.author |
Bonifaci, 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 |
2018-09-03T14:04:58Z |
dc.date |
2018-09-03T14:04:58Z |
dc.date |
2011-04-05 |
dc.date |
2018-09-03T14:04:59Z |
dc.identifier.citation |
1465-542X |
dc.identifier.citation |
595975 |
dc.identifier.uri |
http://hdl.handle.net/2445/124234 |
dc.format |
14 p. |
dc.format |
application/pdf |
dc.language.iso |
eng |
dc.publisher |
BioMed Central |
dc.relation |
Reproducció del document publicat a: https://doi.org/10.1186/bcr2862 |
dc.relation |
Breast Cancer Research, 2011, vol. 13, num. R40 |
dc.relation |
https://doi.org/10.1186/bcr2862 |
dc.rights |
cc-by (c) Martrat, Griselda et al., 2011 |
dc.rights |
info:eu-repo/semantics/openAccess |
dc.rights |
http://creativecommons.org/licenses/by/3.0/es |
dc.subject |
Càncer de mama |
dc.subject |
Anèmia aplàstica |
dc.subject |
Breast cancer |
dc.subject |
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.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. |