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:

Deficiency in BRCA2 leads to increase in non-conservative homologous recombination

Oncogene volume 21, pages 5188–5192 (2002)Cite this article

Abstract

The BRCA2 tumor suppressor has been implicated in the maintenance of genomic integrity through a function in cellular responses to DNA damage. The BRCA2 protein directly associates with Rad51, that is essential for repair of double-strand breaks (DSBs) by homologous recombination (HR). In this report, we study the BRCA2-defective Chinese hamster cell mutant V-C8 for its ability to perform homology-directed repair (HDR) between repeated sequences. V-C8 cells were recently shown to be defective in Rad51 foci formation in response to DNA damage. Strikingly, we find that these BRCA2 mutant cells exhibit a strong stimulation of HDR activity compared to the V79 parental cells, which harbor a wild-type BRCA2. Furthermore, molecular characterization of the HDR products shows that loss of BRCA2 in V-C8 cells leads to significant reduction in Rad51-dependent gene conversion but strong enhancement of Rad51-independent single-strand annealing (SSA) events frequency. These data imply that, when HDR by conservative gene conversion is impaired, DSBs usually repaired by this pathway are instead resolved by other non-conservative HDR subpathways. Therefore, high chromosomal instability in BRCA2-deficient cells presumably results from enhancement of error-prone repair mechanisms, such as SSA.

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

Similar content being viewed by others

References

  • Baumann P, West SC . 1998 Trends Biochem. Sci. 23: 247–251

  • Capizzi RL, Jameson JW . 1973 Mutation Res. 17: 147–148

  • Connor F, Bertwistle D, Mee PJ, Ross GM, Swift S, Grigorieva E, Tybulewicz VL, Ashworth A . 1997 Nat. Genet. 17: 423–430

  • Davies AA, Masson JY, McIlwraith MJ, Stasiak AZ, Stasiak A, Venkitaraman AR, West SC . 2001 Mol. Cell. 7: 273–282

  • De Silva IU, McHugh PJ, Clingen PH, Hartley JA . 2000 Mol. Cell. Biol. 20: 7980–7990

  • Dronkert MLG, Kanaar R . 2001 Mutation Res. 486: 217–247

  • Haaf T, Golub EI, Reddy G, Radding CM, Ward DC . 1995 Proc. Natl. Acad. Sci. USA 92: 2298–2302

  • Johnson RD, Jasin M . 2000 EMBO J. 19: 3398–3407

  • Kraakman-van der Zwet M, Overkamp WJ, van Lange RE, Essers J, van Duijn-Goedhart A, Wiggers I, Swaminathan S, van Buul PP, Errami A, Tan RT, Jaspers NG, Sharan SK, Kanaar R, Zdzienicka MZ . 2002 Mol. Cell. Biol. 22: 669–679

  • Lambert S, Lopez BS . 2000 EMBO J. 19: 3090–3099

  • 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, Thompson LH . 1998 Mol. Cell. 1: 783–793

  • Meyn MS . 1993 Science 260: 1327–1330

  • Moynahan ME, Pierce AJ, Jasin M . 2001 Mol. Cell. 7: 263–272

  • Overkamp WJI, Rooimans MA, Neuteboom I, Telleman P, Arwert F, Zdzienicka MZ . 1993 Somat. Cell Mol. Genet. 19: 431–437

  • Papouli E, Lafon C, Valette A, Zdzienicka MZ, Defais M, Larminat F . 2000 Biochem. Pharmacol. 59: 1101–1107

  • Patel KJ, Yu VP, Lee H, Corcoran A, Thistlethwaite FC, Evans MJ, Colledge WH, Friedman LS, Ponder BA, Venkitaraman AR . 1998 Mol. Cell. 1: 347–357

  • Richardson C, Jasin M . 2000 Nature 405: 697–700

  • Sharan SK, Morimatsu M, Albrecht U, Lim DS, Regel E, Dinh C, Sands A, Eichele G, Hasty P, Bradley A . 1997 Nature 386: 804–810

  • Sonoda E, Sasaki MS, Buerstedde JM, Bezzubova O, Shinohara A, Ogawa H, Takata M, Yamaguchi-Iwai Y, Takeda S . 1998 EMBO J. 17: 598–608

  • Sonoda E, Sasaki MS, Morrison C, Yamaguchi-Iwai Y, Takata M, Takeda S . 1999 Mol. Cell Biol. 19: 5166–5169

  • Tashiro S, Walter J, Shinohara A, Kamada N, Cremer T . 2000 J. Cell Biol. 150: 283–291

  • Tavtigian SV, Simard J, Rommens J, Couch F, Shattuck-Eidens D, Neuhausen S, Merajver S, Thorlacius S, Offit K, Stoppa-Lyonnet D, Belanger C, Bell R, Berry S, Bogden R, Chen Q, Davis T, Dumont M, Frye C, Hattier T, Jammulapati S, Janecki T, Jiang P, Kehrer R, Leblanc JF, Mitchell JT, McArthur-Morrison J, Nguyen K, Peng Y, Samson C, Schroeder M, Snyder SC, Steele L, Stringfellow M, Stroup C, Swedlund B, Swenson J, Teng D, Thomas A, Tran T, Tranchant M, Weaver-Feldhaus J, Wong AKC, Shizuya H, Eyfjord JE, Cannon-Albright L, Labrie F, Skolnick MH, Weber B, Kamb A, Goldgar DE . 1996 Nat. Genet. 12: 333–337

  • Tutt A, Bertwistle D, Valentine J, Gabriel A, Swift S, Ross G, Griffin C, Thacker J, Ashworth A . 2001 EMBO J. 17: 4704–4716

  • Tutt A, Gabriel A, Bertwistle D, Connor F, Paterson H, Peacock J, Ross G, Ashworth A . 1999 Curr. Biol. 9: 1107–1110

  • Verhaegh GWCT, Jongmans W, Morolli B, Jaspers NGJ, van der Schans GP, Lohman PHM, Zdzienicka MZ . 1995 Mutation Res. 337: 119–129

  • Vispé S, Cazaux C, Lesca C, Defais M . 1998 Nucleic Acids Res. 26: 2859–2864

  • Wooster R, Neuhausen SL, Mangion J, Quirk Y, Ford D, Collins N, Nguyen K, Seal S, Tran T, Averill D, Fields P, Marshall G, Narod S, Lenoir GM, Lynch H, Feunteun J, Devilee P, Cornelisse CJ, Menko FH, Daly PA, Ormiston W, McManus R, Pye C, Lewis CM, Cannon-Albright LA, Peto J, Ponder BAJ, Skolnick MH, Easton DF, Goldgar DE, Stratton MR . 1994 Science 265: 2088–2090

  • Yu VP, Koehler M, Steinlein C, Schmid M, Hanakahi LA, van Gool AJ, West SC, Venkitaraman AR . 2000 Genes Dev. 14: 1400–1406

  • Yuan SS, Lee SY, Chen G, Song M, Tomlinson GE, Lee EY . 1999 Cancer Res. 59: 3547–3551

  • Zdzienicka MZ, Arwert F, Neuteboom I, Rooimans M, Simons JWIM . 1990 Somat. Cell. Mol. Genet. 6: 575–581

  • Zhang LH, Vrieling H, van Zeeland AA, Jenssen D . 1992 J. Mol. Biol. 223: 627–635

Download references

Acknowledgements

We thank Dr MZ Zdzienicka for generously providing us with the V-C8 cell line and Dr S Meyn for providing the pNeoA vector. This work was supported by the Association pour la Recherche sur le Cancer grant 9238.

Author information

Authors and Affiliations

  1. Institut de Pharmacologie et de Biologie Structurale, UMR 5089, C.N.R.S., 205, Route de Narbonne, Toulouse, Cedex 4, 31077, France

    Florence Larminat, Maryse Germanier, Efterpi Papouli & Martine Defais

Authors
  1. Florence Larminat
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maryse Germanier
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Efterpi Papouli
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Martine Defais
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Florence Larminat.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Larminat, F., Germanier, M., Papouli, E. et al. Deficiency in BRCA2 leads to increase in non-conservative homologous recombination. Oncogene 21, 5188–5192 (2002). https://doi.org/10.1038/sj.onc.1205659

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1205659

Keywords

This article is cited by

Search

Advanced search

Quick links