Browse > Article

Essential Role of brc-2 in Chromosome Integrity of Germ Cells in C. elegans  

Ko, Eunkyong (Department of Biological Sciences and Institute of Molecular Biology and Genetics, Seoul National University)
Lee, Junho (Department of Biological Sciences and Institute of Molecular Biology and Genetics, Seoul National University)
Lee, Hyunsook (Department of Biological Sciences and Institute of Molecular Biology and Genetics, Seoul National University)
Publication Information
Molecules and Cells / v.26, no.6, 2008 , pp. 590-594 More about this Journal
Abstract
brc-2, an ortholog of BRCA2 in Caenorhabditis elegans, is essential in the maintenance of genetic integrity. In C. elegans, cellular location correlates with meiotic progression, and transgene-induced cosuppression is observed in the germ line but not in somatic cells. We used these unique features to dissect the role of brc-2 in the germ line from that in somatic cells. In situ hybridization of wild type animals revealed that brc-2 gene expression was higher in oocytes than in other germline cells, and was barely detectable in mitotic cells. In contrast, germ cells containing multicopies of the brc-2 transgene showed no significant in situ hybridization signal at any oogenesis stage, confirming that brc-2 expression was functionally cosuppressed in the transgenic germ line. RAD-51 foci formation in response to DNA damage was abrogated in brc-2-cosuppressed germ cells, whereas wild-type germ cells showed strong RAD-51 foci formation. These germ cells exhibited massive chromosome fragmentation and decompaction instead of six bivalent chromosomes in diakinesis. Accordingly, lethality was observed after the early stage of germline development. These results suggest that brc-2 plays essential roles in chromosome integrity in early prophase, and therefore is crucial in meiotic progression and embryonic survival.
Keywords
brc-2; C. elegans; chromosome integrity; cosuppression; germ cells;
Citations & Related Records

Times Cited By Web Of Science : 3  (Related Records In Web of Science)
연도 인용수 순위
  • Reference
1 Wicky, C., Alpi, A, Passannante, M., Rose, A, Gartner, A, and Muller, F. (2004). Multiple genetic pathways involving the Caenorhabditis elegans Bloom's syndrome genes him-6, rad-51, and top-3 are needed to maintain genome stability in the germ line. Mol. Cell. BioI. 24, 5016-5027   DOI   ScienceOn
2 Yu, V.P., Koehler, M., Steinlein, C., Schmid, M., Hanakahi, L.A, van Gool, AJ., West, S.C., and Venkitaraman, AR. (2000). Gross chromosomal rearrangements and genetic exchange between nonhomologous chromosomes following BRCA2 inactivation. Genes Dev. 14,1400-1406
3 Dernburg, AF., Zalevsky, J., Colaiacovo, M.P., and Villeneuve, AM. (2000). Transgene-mediated cosuppression in the C. elegans germ line. Genes Dev. 14,1578-1583
4 Jedrusik, MA, and Schulze, E. (2001). A single histone H1 isoform (H1.1) is essential for chromatin silencing and germline development in Caenorhabditis elegans. Development 128, 1069-1080
5 Patel, K.J., Yu, V.P., Lee, H., Corcoran, A, Thistlethwaite, F.C., Evans, M.J., Colledge, W.H., Friedman, L.S., Ponder, BA, and Venkitaraman, AR. (1998). Involvement of Brca2 in DNA repair. Mol. Cell 1,347-357   DOI   ScienceOn
6 Venkitaraman, AR. (2002). Cancer susceptibility and the functions of BRCA1 and BRCA2. Cell 108,171-182   DOI   ScienceOn
7 Petalcorin, M.I., Sandall, J., Wigley, D. B., and Boulton, S.J. (2006). CeBRC-2 stimulates D-Ioop formation by RAD-51 and promotes DNA single-strand annealing. J. Mol. BioI. 361, 231-242   DOI   ScienceOn
8 Yang, H., Jeffrey, p.o., Miller, J., Kinnucan, E., Sun, Y., Thoma, N.H., Zheng, N., Chen, P.L., Lee, W.H., and Pavletich, N.P. (2002). BRCA2 function in DNA binding and recombination from a BRCA2-DSS1-ssDNA structure. Science 297,1837-1848   DOI   ScienceOn
9 Pellegrini, L., and Venkitaraman, A (2004). Emerging functions of BRCA2 in DNA recombination. Trends Biochem. Sci. 29, 310-316   DOI   ScienceOn
10 Yang, H., Li, Q., Fan, J., Holloman, WK, and Pavletich, N.P. (2005). The BRCA2 homologue Brh2 nucleates RAD51 filament formation at a dsDNA-ssDNA junction. Nature 433, 653-657   DOI   ScienceOn
11 Shivji, MK, and Venkitaraman, AR. (2004). DNA recombination, chromosomal stability and carcinogenesis: insights into the role of BRCA2. DNA Repair. 3, 835-843   DOI   ScienceOn
12 Li, Y., Kelly, W.G., Logsdon, J.M., Jr., Schurko, AM., Harfe, B.D., Hill-Harte, K.L., and Kahn, RA (2004). Functional genomic analysis of the ADP-ribosylation factor family of GTPases: phylogeny among diverse eukaryotes and function in C. elegans. FASEBJ. 18,1834-1850   DOI   ScienceOn
13 Petalcorin, M.I., Galkin, V.E., Yu, X., Egelman, E.H., and Boulton, S.J. (2007). Stabilization of RAD-51-DNA filaments via an interaction domain in Caenorhabditis elegans BRCA2. Proc. Natl. Acad. Sci. USA 104,8299-8304
14 Venkitaraman, AR. (2001). Chromosome stability, DNA recombination and the BRCA2 tumour suppressor. Curr. Opin. Cell BioI. 13, 338-343   DOI   ScienceOn
15 Alpi, A, Pasierbek, P., Gartner, A, and Loidl, J. (2003). Genetic and cytological characterization of the recombination protein RAD-51 in Caenorhabditis elegans. Chromosoma. 112, 6-16   DOI
16 Adamo, A, Montemauri, P., Silva, N., Ward, J.D., Boulton, S.J., and La Volpe, A (2008). BRC-1 acts in the inter-sister pathway of meiotic double-strand break repair. EMBO Rep. 9, 287-292   DOI   ScienceOn
17 Wu, L. (2008). Wrestling off RAD51: a novel role for RecQ helicases. Bioessays 30, 291-295   DOI   ScienceOn
18 Joeng, K.S., Song, E.J., Lee, K.J. and Lee, J. (2004). Long lifespan in worms with long telomeric DNA Nat. Genet. 36, 607-611   DOI   ScienceOn
19 Min, J., Park, P.G., Ko, E., Choi, E., and Lee, H. (2007). Identification of Rad51 regulation by BRCA2 using Caenorhabditis elegans BRCA2 and bimolecular fluorescence complementation analysis. Biochem. Biophys. Res. Commun. 362, 958-964   DOI   ScienceOn
20 Pellegrini, L., Yu, D.S., Lo, T., Anand, S., Lee, M., Blundell, T.L., and Venkitaraman, AR. (2002). Insights into DNA recombination from the structure of a RAD51-BRCA2 complex. Nature 420, 287-293   DOI   ScienceOn
21 West, S.C. (2003). Molecular views of recombination proteins and their control. Nat. Rev. Mol. Cell BioI. 4, 435-445   DOI   ScienceOn
22 Rinaldo, C., Bazzicalupo, P., Ederle, S., Hilliard, M., and La Volpe, A (2002). Roles for Caenorhabditis elegans rad-51 in meiosis and in resistance to ionizing radiation during development. Genetics 160,471-479
23 Martin, J.S., Winkelmann, N., Petalcorin, M.I., Mcllwraith, M.J., and Boulton, S.J. (2005). RAD-51-dependent and -independent roles of a Caenorhabditis elegans BRCA2-related protein during DNA double-strand break repair. Mol. Cell. BioI. 25, 3127-3139   DOI   ScienceOn
24 Takanami, T., Mori, A, Takahashi, H., Horiuchi, S., and Higashitani, A (2003). Caenorhabditis elegans Ce-rdh-1/rad-51 functions after double-strand break formation of meiotic recombination. Chromosome Res. 11,125-135   DOI   ScienceOn