%0 Journal Article
%T Exploring the link between MORF4L1 and risk of breast cancer
%A Griselda Martrat
%A Christopher A Maxwell
%A Emiko Tominaga
%A Montserrat Porta-de-la-Riva
%A N¨²ria Bonifaci
%A Laia G¨®mez-Bald¨®
%A Massimo Bogliolo
%A Conxi L¨¢zaro
%A Ignacio Blanco
%A Joan Brunet
%A Helena Aguilar
%A Juana Fern¨¢ndez-Rodr¨ªguez
%A Sheila Seal
%A Anthony Renwick
%A Nazneen Rahman
%A Julia K¨¹hl
%A Kornelia Neveling
%A Detlev Schindler
%A Mar¨ªa J Ram¨ªrez
%A Mar¨ªa Castell¨¤
%A Gonzalo Hern¨¢ndez
%A EMBRACE
%A Douglas F Easton
%A Susan Peock
%A Margaret Cook
%A Clare T Oliver
%A Debra Frost
%A Radka Platte
%A D Gareth Evans
%A Fiona Lalloo
%J Breast Cancer Research
%D 2011
%I BioMed Central
%R 10.1186/bcr2862
%X 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.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 ¦Ã-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.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.Genes that when mutated cause Fanconi anemia (FA) and/or influence bre
%U http://breast-cancer-research.com/content/13/2/R40