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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Camerini-otero, R. Daniel Ichijima, Yosuke Lee, Jeannie T. Andreassen, Paul R. Namekawa, Satoshi H. Alavattam, Kris G. Broering, Tyler J. Sadreyev, Ruslan I. Hasegawa, Kazuteru Kato, Yasuko |
| Description | Author Affiliation: Broering TJ ( Division of Reproductive Sciences and Division of Developmental Biology, Perinatal Institute, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229Division of Reproductive Sciences and Division of Developmental Biology, Perinatal); Alavattam KG ( Division of Reproductive Sciences and Division of Developmental Biology, Perinatal Institute, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229Division of Reproductive Sciences and Division of Developmental Biology, Perinatal); Sadreyev RI ( Howard Hughes Medical Institute, Department of Molecular Biology, Massachusetts General Hospital, Department of Pathology, and Department of Genetics, Harvard Medical School, Boston, MA 02114 Howard Hughes Medical Institute, Department of Molecular Biology, Massachusetts General Hospital, Department); Ichijima Y ( Division of Reproductive Sciences and Division of Developmental Biology, Perinatal Institute, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229Division of Reproductive Sciences and Division of Developmental Biology, Perinatal); Kato Y ( Division of Reproductive Sciences and Division of Developmental Biology, Perinatal Institute, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229Division of Reproductive Sciences and Division of Developmental Biology, Perinatal); Hasegawa K ( Division of Reproductive Sciences and Division of Developmental Biology, Perinatal Institute, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229Division of Reproductive Sciences and Division of Developmental Biology, Perinatal); Camerini-Otero RD ( Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.); Lee JT ( Howard Hughes Medical Institute, Department of Molecular Biology, Massachusetts General Hospital, Department of Pathology, and Department of Genetics, Harvard Medical School, Boston, MA 02114 Howard Hughes Medical Institute, Department of Molecular Biology, Massachusetts General Hospital, Department); Andreassen PR ( Division of Reproductive Sciences and Division of Developmental Biology, Perinatal Institute, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229 Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnat); Namekawa SH ( Division of Reproductive Sciences and Division of Developmental Biology, Perinatal Institute, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229Division of Reproductive Sciences and Division of Developmental Biology, Perinatal) |
| Abstract | During meiosis, DNA damage response (DDR) proteins induce transcriptional silencing of unsynapsed chromatin, including the constitutively unsynapsed XY chromosomes in males. DDR proteins are also implicated in double strand break repair during meiotic recombination. Here, we address the function of the breast cancer susceptibility gene Brca1 in meiotic silencing and recombination in mice. Unlike in somatic cells, in which homologous recombination defects of Brca1 mutants are rescued by 53bp1 deletion, the absence of 53BP1 did not rescue the meiotic failure seen in Brca1 mutant males. Further, BRCA1 promotes amplification and spreading of DDR components, including ATR and TOPBP1, along XY chromosome axes and promotes establishment of pericentric heterochromatin on the X chromosome. We propose that BRCA1-dependent establishment of X-pericentric heterochromatin is critical for XY body morphogenesis and subsequent meiotic progression. In contrast, BRCA1 plays a relatively minor role in meiotic recombination, and female Brca1 mutants are fertile. We infer that the major meiotic role of BRCA1 is to promote the dramatic chromatin changes required for formation and function of the XY body. |
| ISSN | 00219525 |
| e-ISSN | 15408140 |
| Journal | The Journal of Cell Biology |
| Issue Number | 5 |
| Volume Number | 205 |
| Language | English |
| Publisher | Rockefeller University Press (United States) |
| Publisher Date | 2014-06-09 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | BRCA1 Protein Physiology DNA Damage Heterochromatin Genetics Meiosis Recombination, Genetic X Chromosome Alleles Animals Chromosome Pairing Chromosomes Metabolism Exons Gene Deletion Gene Silencing Mice Mutation Phenotype Spermatogenesis Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Cell Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine |
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