Male fertility defect associated with disrupted BRCA1-PALB2 interaction in mice Journal Article
| Authors: | Simhadri, S.; Peterson, S.; Patel, D. S.; Huo, Y.; Cai, H.; Bowman-Colin, C.; Miller, S.; Ludwig, T.; Ganesan, S.; Bhaumik, M.; Bunting, S. F.; Jasin, M.; Xia, B. |
| Article Title: | Male fertility defect associated with disrupted BRCA1-PALB2 interaction in mice |
| Abstract: | PALB2 links BRCA1 and BRCA2 in homologous recombinational repair of DNA double strand breaks (DSBs). Mono-allelic mutations in PALB2 increase the risk of breast, pancreatic, and other cancers, and biallelic mutations cause Fanconi anemia (FA). Like Brca1 and Brca2, systemic knock-out of Palb2 in mice results in embryonic lethality. In this study, we generated a hypomorphic Palb2 allele expressing a mutant PALB2 protein unable to bind BRCA1. Consistent with an FA-like phenotype, cells from the mutant mice showed hypersensitivity and chromosomal breakage when treated with mitomycin C, a DNA interstrand crosslinker. Moreover, mutant males showed reduced fertility due to impaired meiosis and increased apoptosis in germ cells. Interestingly, mutant meiocytes showed a significant defect in sex chromosome synapsis, which likely contributed to the germ cell loss and fertility defect. Our results underscore the in vivo importance of the PALB2-BRCA1 complex formation in DSB repair and male meiosis. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc. |
| Keywords: | cell death; mammals; crosslinker; chromosomes; embryonic lethality; repair; male fertility; defects; dna double strand breaks; sex chromosomes; biallelic mutations; complex formations; fanconi anemias |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 289 |
| Issue: | 35 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 2014-08-29 |
| Start Page: | 24617 |
| End Page: | 24629 |
| Language: | English |
| DOI: | 10.1074/jbc.M114.566141 |
| PROVIDER: | scopus |
| PMCID: | PMC4148885 |
| PUBMED: | 25016020 |
| DOI/URL: | |
| Notes: | Export Date: 1 October 2014 -- Source: Scopus |
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