Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Short Report
  • Published:

Genetic interactions between RAD51 and its paralogues for centrosome fragmentation and ploidy control, independently of the sensitivity to genotoxic stresses

Oncogene volume 24, pages 3691–3696 (2005)Cite this article

Abstract

We evaluate here whether RAD51 and its paralogues XRCC2 and XRCC3 act via a common pathway for sensitivity to genotoxic stress, centrosome fragmentation and chromosome stability. We expressed the RAD51 dominant-negative SMRAD51 in irs1 and irs1SF cells, defective for XRCC2 and XRCC3, respectively, and in their corresponding wild-type cells (V79 and AA8, respectively). V79-SMRAD51 cells are sensitive to mitomycin C (MMC), but SMRAD51 did not further sensitize irs1 cells to MMC, showing that SMRAD51 and XRCC2 act on the same pathway for resistance to MMC. However, in contrast to irs1 and irs1SF cells, SMRAD51-V79 and SMRAD51-AA8 cells are not sensitive to γ-rays or UV-C. Despite these differences in sensitivity, SMRAD51-expressing cells and xrcc2- or xrcc3-defective cells show similar increased levels of centrosome fragmentation. This spontaneous centrosome fragmentation is resistant to caffeine, suggesting that ATM and ATR are not involved. Consistent with centrosome fragmentation, increased aneuploidy was measured in irs1 and SMRAD51-expressing cells. Expression of SMRAD51 in irs1 or irs1SF cells did not increase further the frequency of multipolar cells. Thus, RAD51, XRCC2 and XRCC3 act in the same pathway for centrosome fragmentation, independently of the sensitivity to exogenous genotoxic stresses and of the ATM/ATR pathway.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  • Asaad NA, Zeng ZC, Guan J, Thacker J and Iliakis G . (2000). Oncogene, 19, 5788–5800.

  • Ausubel F, Brent R, Kingston R, Moore D, Seidman J, Smith J and Struhl K . (1999). Current Protocols in Molecular Biology. John Wiley & Sons Inc.: Boston, MA.

    Google Scholar 

  • Bertrand P, Lambert S, Joubert C and Lopez BS . (2003). Oncogene, 22, 7587–7592.

  • Bertrand P, Saintigny Y and Lopez BS . (2004). Trends Genet., 20, 235–243.

  • Bishop DK, Ear U, Bhattacharyya A, Calderone C, Beckett M, Weichselbaum RR and Shinohara A . (1998). J. Biol. Chem., 273, 21482–21488.

  • Block WD, Merkle D, Meek K and Lees-Miller SP . (2004). Nucleic Acids Res., 32, 1967–1972.

  • Brenneman MA, Wagener BM, Miller CA, Allen C and Nickoloff JA . (2002). Mol. Cell, 10, 387–395.

  • Cox MM, Goodman MF, Kreuzer KN, Sherratt DJ, Sandler SJ and Marians KJ . (2000). Nature, 404, 37–41.

  • Fuller LF and Painter RB . (1988). Mutat. Res., 193, 109–121.

  • Gangloff S, Soustelle C and Fabre F . (2000). Nat. Genet., 25, 192–194.

  • Griffin CS, Simpson PJ, Wilson CR and Thacker J . (2000). Nat. Cell Biol., 2, 757–761.

  • Henry-Mowatt J, Jackson D, Masson JY, Johnson PA, Clements PM, Benson FE, Thompson LH, Takeda S, West SC and Caldecott KW . (2003). Mol. Cell, 11, 1109–1117.

  • Hinchcliffe EH and Sluder G . (2001). Genes Dev., 15, 1167–1181.

  • Hut HM, Lemstra W, Blaauw EH, Van Cappellen GW, Kampinga HH and Sibon OC . (2003). Mol. Cell. Biol., 14, 1993–2004.

  • Johnson RD, Liu N and Jasin M . (1999). Nature, 401, 397–399.

  • Jones NJ, Cox R and Thacker J . (1987). Mutat. Res., 183, 279–286.

  • Kans JA and Mortimer RK . (1991). Gene, 105, 139–140.

  • Lambert S and Lopez BS . (2000). EMBO J., 19, 3090–3099.

  • Lambert S and Lopez BS . (2001). Oncogene, 20, 6627–6631.

  • Lambert S and Lopez BS . (2002). Oncogene, 21, 4065–4069.

  • Linke SP, Sengupta S, Khabie N, Jeffries BA, Buchhop S, Miska S, Henning W, Pedeux R, Wang XW, Hofseth LJ, Yang Q, Garfield SH, Sturzbecher HW and Harris CC . (2003). Cancer Res., 63, 2596–2605.

  • Liu N, Lamerdin JE, Tebbs RS, Schild D, Tucker JD, Shen MR, Brookman KW, Siciliano MJ, Walter CA, Fan W, Narayana LS, Zhou ZQ, Adamson AW, Sorensen KJ, Chen DJ, Jones NJ and Thompson LH . (1998). Mol. Cell, 1, 783–793.

  • Liu N, Schild D, Thelen MP and Thompson LH . (2002). Nucleic Acids Res., 30, 1009–1015.

  • Liu Y, Masson JY, Shah R, O'Regan P and West SC . (2004). Science, 303, 243–246.

  • Lovett ST . (1994). Gene, 142, 103–106.

  • Masson JY, Tarsounas MC, Stasiak AZ, Stasiak A, Shah R, McIlwraith MJ, Benson FE and West SC . (2001). Genes Dev., 15, 3296–3307.

  • Michel B, Flores MJ, Viguera E, Grompone G, Seigneur M and Bidnenko V . (2001). Proc. Natl. Acad. Sci. USA, 98, 8181–8188.

  • O'Regan P, Wilson C, Townsend S and Thacker J . (2001). J. Biol. Chem., 276, 22148–22153.

  • Pierce AJ, Johnson RD, Thompson LH and Jasin M . (1999). Genes Dev., 13, 2633–2638.

  • Saintigny Y, Delacote F, Vares G, Petitot F, Lambert S, Averbeck D and Lopez BS . (2001). EMBO J., 20, 3861–3870.

  • Saintigny Y and Lopez BS . (2002). Oncogene, 21, 488–492.

  • Saintigny Y, Makienko K, Swanson C, Emond MJ and Monnat Jr RJ . (2002). Mol. Cell. Biol., 22, 6971–6978.

  • Sarkaria JN, Busby EC, Tibbetts RS, Roos P, Taya Y, Karnitz LM and Abraham RT . (1999). Cancer Res., 59, 4375–4382.

  • Sung P . (1997). Genes Dev., 11, 1111–1121.

  • Thacker J . (1999). Trends Genet., 15, 166–168.

  • Wang H, Boecker W, Wang X, Guan J, Thompson LH, Nickoloff JA and Iliakis G . (2004). Oncogene, 23, 824–834.

Download references

Acknowledgements

We thanks Drs P Bertrand, F Lebrun and D Marsh for helpful discussion and critical reading of the manuscript. This work was supported by the collaborative program CEA-DSV/Institut Curie, Electricité de France and la Ligue Nationale contre le Cancer, ‘Equipe labellisée’.

Author information

Authors and Affiliations

  1. UMR CNRS/CEA 217, Direction des Sciences du Vivant, Département de Radiobiologie et Radiopathologie, 18 route du Panorama, PO Box 06, Bat 05, 92265, Fontenay-aux-Roses Cedex, France

    Fayza Daboussi & Bernard S Lopez

  2. Medical Research Council, Radiation & Genome Stability Unit, Harwell, Oxfordshire, OX11 0RD, England

    John Thacker

Authors
  1. Fayza Daboussi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. John Thacker
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bernard S Lopez
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bernard S Lopez.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Daboussi, F., Thacker, J. & Lopez, B. Genetic interactions between RAD51 and its paralogues for centrosome fragmentation and ploidy control, independently of the sensitivity to genotoxic stresses. Oncogene 24, 3691–3696 (2005). https://doi.org/10.1038/sj.onc.1208438

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1208438

Keywords

This article is cited by

Search

Advanced search

Quick links