Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Deficiency of Bloom's Syndrome Protein Causes Hypersensitivity of C. elegans to Ionizing Radiation but Not to UV Radiation, and Induces p53-dependent Physiological Apoptosis

  • Kim, Yun Mi (Department of Biochemistry, College of Science, Yonsei University) ;
  • Yang, Insil (Department of Biochemistry, College of Science, Yonsei University) ;
  • Lee, Jiyeung (Department of Biochemistry, College of Science, Yonsei University) ;
  • Koo, Hyeon-Sook (Department of Biochemistry, College of Science, Yonsei University)
  • Received : 2005.05.06
  • Accepted : 2005.07.08
  • Published : 2005.10.31
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Abstract

Caenorhabditis elegans him-6 mutants, which show a high incidence of males and partial embryonic lethality, are defective in the orthologue of human Bloom's syndrome protein (BLM). When strain him-6(e1104) containing a missense him-6 mutation was irradiated with ${\gamma}$-rays during germ cell development or embryogenesis, embryonic lethality was higher than in the wild type, suggesting a critical function of the wild type gene in mitotic and pachytene stage germ cells as well as in early embryos. Even in the absence of ${\gamma}$-irradiation, apoptosis was elevated in the germ cells of the him-6 strain and this increase was dependent on a functional p53 homologue (CEP-1), suggesting that spontaneous DNA damage accumulates due to him-6 deficiency. However, induction of germline apoptosis by ionizing radiation was not significantly affected by the deficiency, indicating that HIM-6 has no role in the induction of apoptosis by exogenous DNA damage. We conclude that the C. elegans BLM orthologue is involved in DNA repair in promeiotic cells undergoing homologous recombination, as well as in actively dividing germline and somatic cells.

Keywords

Acknowledgement

Supported by : Ministry of Health & Welfare

References

  1. Ababou, M., Dumaire, V., Lecluse, Y., and Amor-Gueret, M. (2002) Cleavage of BLM and sensitivity of Bloom's syndrome cells to hydroxyurea and UV-C radiation. Cell Cycle 1, 262-266
  2. Bischof, O., Kim, S. H., Irving, J., Beresten, S., Ellis, N. A., et al. (2001) Regulation and localization of the Bloom syndrome protein in response to DNA damage. J. Cell Biol. 153, 367-380 https://doi.org/10.1083/jcb.153.2.367
  3. Chester, N., Kuo, F., Kozak, C., O'Hara, C. D., and Leder, P. (1998) Stage-specific apoptosis, developmental delay, and embryonic lethality in mice homozygous for a targeted disruption in the murine Bloom's syndrome gene. Genes Dev. 12, 3382-3393 https://doi.org/10.1101/gad.12.21.3382
  4. Davalos, A. R. and Campisi, J. (2003) Bloom syndrome cells undergo p53-dependent apoptosis and delayed assembly of BRCA1 and NBS1 repair complexes at stalled replication forks. J. Cell Biol. 162, 1197-1209 https://doi.org/10.1083/jcb.200304016
  5. Ellis, N. A., Groden, J., Ye, T.-Z., Straughen, J., Lennon, D. J., et al. (1995) The Bloom's syndrome gene product is homologous to RecQ helicases. Cell 83, 655-666 https://doi.org/10.1016/0092-8674(95)90105-1
  6. Frei, C. and Gasser, S. M. (2000) RecQ-like helicases: the DNA replication checkpoint connection. J. Cell Sci. 113, 2641-2646
  7. Gumienny, T. L., Lambie, E., Hartwieg, E., Horvitz, H. R., and Hengartner, M. O. (1999) Genetic control of programmed cell death in the Caenorhabditis elegans hermaphrodite germline. Development 126, 1011-1022
  8. Hodgkin, J., Horvitz, R., and Brenner, S. (1979) Nondisjunction mutants of the nematode Caenorhabditis elegans. Genetics 91, 67-94
  9. Imamura, O., Fujita, K., Shimamoto, A., Tanabe, H., Takeda, S., et al. (2001) Bloom helicase is involved in DNA surveillance in early S phase in vertebrate cells. Oncogene 20, 1143-1151 https://doi.org/10.1038/sj.onc.1204195
  10. Jeong, Y. S., Kang, Y. l., Lim, K. H., Lee, M. H., Lee, J., et al. (2003) Deficiency of Caenorhabditis elegans RecQ5 homologue reduces life span and increases sensitivity to ionizing radiation. DNA Repair 2, 1309-1319 https://doi.org/10.1016/j.dnarep.2003.07.003
  11. Karow, J. K., Wu, L., and Hickson, I. D. (2000) RecQ family helicases: roles in cancer and aging. Curr. Opin. Genet. Dev. 10, 32-38 https://doi.org/10.1016/S0959-437X(99)00039-8
  12. Kim, Y. C., Lee, M. H., Ryu, S. S., Kim, J. H., and Koo, H. S. (2002) Coaction of DNA topoisomerase III$\alpha$ and a RecQ homologue during the germ-line mitosis in Caenorhabditis elegans. Genes Cells 7, 19-27 https://doi.org/10.1046/j.1356-9597.2001.00496.x
  13. Kitao, S., Shimamoto, A., Goto, M., Miller, R. W., Smithson, W. A., et al. (1999) Mutations in RECQL4 cause a subset of cases of Rothmund-Thomson syndrome. Nat. Genet. 22, 82-84 https://doi.org/10.1038/8788
  14. Krepinsky, A. B., Rainbow, A. J., and Heddle, J. A. (1980) Studies on the ultraviolet light sensitivity of Bloom's syndrome fibroblasts. Mutat. Res. 69, 357-368 https://doi.org/10.1016/0027-5107(80)90100-1
  15. Lee, S.-J., Yook, J.-S., Han, S. M., and Koo, H.-S. (2004) A Werner syndrome protein homologue affects C. elegans development, growth rate, life span, and sensitivity to DNA damage by acting at a DNA damage checkpoint. Development 131, 2565-2575 https://doi.org/10.1242/dev.01136
  16. Moens, P. B., Freire, R., Tarsounas, M., Spyropoulos, B., and Jackson, S. P. (2000) Expression and nuclear localization of BLM, a chromosome stability protein mutated in Bloom's syndrome, suggest a role in recombination during meiotic prophase. J. Cell Sci. 113, 663-672
  17. Puranam, K. L. and Blackshear, P. J. (1994) Cloning and characterization of RecQL, a potential human homologue of the Escherichia coli DNA helicase RecQ. J. Biol. Chem. 269, 29838-29845
  18. Seki, M., Miyazawa, H., Tada, S., Yanagisawa, J., Yamaoka, T., et al. (1994) Molecular cloning of cDNA encoding human DNA helicase Q1 which has homology to Escherichia coli RecQ helicase and localization of the gene at chromosome 12p12. Nucleic Acids Res. 22, 4566-4573 https://doi.org/10.1093/nar/22.22.4566
  19. Schumahcer, B., Hofmann, K., Boulton, S., and Gartner, A. (2001) The C. elegans homolog of the p53 tumor suppressor is required for DNA damage-induced apoptosis. Curr. Biol. 11, 1722-1727 https://doi.org/10.1016/S0960-9822(01)00534-6
  20. Shimamoto, A., Nishikawa, K., Kitao, S., and Furuichi, Y.(2000) Human $ReeQ5{\beta}$ , a large isomer of RecQ5 DNA helicase, localizes in the nucleoplasm and interacts with topoisomerase $3{\alpha}$ and $3{\betha}$ . Nucleic Acids Res. 28, 1647-1655 https://doi.org/10.1093/nar/28.7.1647
  21. Song, Y.-H. (2005) Drosophila melanogaster: a model for the study of DNA damage checkpoint response. Mol. Cells 19, 167-179
  22. Timmons, L. and Fire, A. (1998) Specific interference by ingested dsRNA. Nature 395, 854 https://doi.org/10.1038/27579
  23. Wang, X. W., Tseng, A., Ellis, N. A., Spillare, E. A., Linke, S. P., et al. (2001) Functional interaction of p53 and BLM DNA helicase in apoptosis. J. Biol. Chem. 276, 32948-32955 https://doi.org/10.1074/jbc.M103298200
  24. Wicky, C., Alpi, A., Passannante, M., Rose, A., Gartner, A., et al. (2004) Multiple genetic pathways involving the Caenorhabditis elegans Bloom's syndrome genes him-6, rad-51, and top-3 are needed to maintain genome stabilityin the germ line. Mol. Cell. Biol. 24, 5016-5027 https://doi.org/10.1128/MCB.24.11.5016-5027.2004
  25. Yu, C.-E., Oshima, J., Fu, Y.-H., Wijsman, E. M., Hisama, F., et al. (1996) Positional cloning of the Werner's syndrome gene. Science 272, 258-262 https://doi.org/10.1126/science.272.5259.258