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.

  • Review
  • Published:

The roles of BRCA1 and BRCA2 and associated proteins in the maintenance of genomic stability

Abstract

The BRCA1 and BRCA2 proteins are important in maintaining genomic stability by promoting efficient and precise repair of double-strand breaks. The main role of BRCA2 appears to involve regulating the function of RAD51 in the repair by homologous recombination. BRCA1 has a broader role upstream of BRCA2, participating in various cellular processes in response to DNA damage. The DNA repair defect associated with mutations in BRCA1 or BRCA2 could be exploited to develop new targeted therapeutic approaches for cancer occurring in mutation carriers.

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

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

Figure 1
Figure 2

Similar content being viewed by others

References

  • Baldeyron C, Jacquemin E, Smith J, Jacquemont C, De Oliveira I, Gad S et al. (2002). Oncogene 21: 1401–1410.

  • Baumeister W, Walz J, Zuhl F, Seemuller E . (1998). Cell 92: 367–380.

  • Bhattacharyya A, Ear US, Koller BH, Weichselbaum RR, Bishop DK . (2000). J Biol Chem 275: 23899–23903.

  • Bignell G, Micklem G, Stratton MR, Ashworth A, Wooster R . (1997). Hum Mol Genet 6: 53–58.

  • Bochar DA, Wang L, Beniya H, Kinev A, Xue Y, Lane WS et al. (2000). Cell 102: 257–265.

  • Bryant HE, Schultz N, Thomas HD, Parker KM, Flower D, Lopez E et al. (2005). Nature 434: 913–917.

  • Chen J, Silver DP, Walpita D, Cantor SB, Gazdar AF, Tomlinson G et al. (1998). Mol Cell 2: 317–328.

  • Cortez D, Wang Y, Qin J, Elledge SJ . (1999). Science 286: 1162–1166.

  • Crackower MA, Scherer SW, Rommens JM, Hui CC, Poorkaj P, Soder S et al. (1996). Hum Mol Genet 5: 571–579.

  • Daniels MJ, Wang Y, Lee M, Venkitaraman AR . (2004). Science 306: 876–879.

  • Dantzer F, de La Rubia G, Menissier-De Murcia J, Hostomsky Z, de Murcia G, Schreiber V . (2000). Biochemistry 39: 7559–7569.

  • Davies AA, Masson JY, McIlwraith MJ, Stasiak AZ, Stasiak A, Venkitaraman AR et al. (2001). Mol Cell 7: 273–282.

  • Deng CX . (2006). Nucleic Acids Res 34: 1416–1426.

  • Dong Y, Hakimi MA, Chen X, Kumaraswamy E, Cooch NS, Godwin AK et al. (2003). Mol Cell 12: 1087–1099.

  • Elliott B, Richardson C, Jasin M . (2005). Mol Cell 17: 885–894.

  • Esashi F, Christ N, Gannon J, Liu Y, Hunt T, Jasin M et al. (2005). Nature 434: 598–604.

  • Evers B, Jonkers J . (2006). Oncogene 25: 5885–5897.

  • Fabbro M, Savage K, Hobson K, Deans AJ, Powell SN, McArthur GA et al. (2004). J Biol Chem 279: 31251–31258.

  • Farmer H, McCabe N, Lord CJ, Tutt AN, Johnson DA, Richardson TB et al. (2005). Nature 434: 917–921.

  • Fedier A, Steiner RA, Schwarz VA, Lenherr L, Haller U, Fink D . (2003). Int J Oncol 22: 1169–1173.

  • Foray N, Marot D, Gabriel A, Randrianarison V, Carr AM, Perricaudet M et al. (2003). EMBO J 22: 2860–2871.

  • Funakoshi M, Li X, Velichutina I, Hochstrasser M, Kobayashi H . (2004). J Cell Sci 117: 6447–6454.

  • Futamura M, Arakawa H, Matsuda K, Katagiri T, Saji S, Miki Y et al. (2000). Cancer Res 60: 1531–1535.

  • Galkin VE, Esashi F, Yu X, Yang S, West SC, Egelman EH . (2005). Proc Natl Acad Sci USA 102: 8537–8542.

  • Gatei M, Scott SP, Filippovitch I, Soronika N, Lavin MF, Weber B et al. (2000). Cancer Res 60: 3299–3304.

  • Gatei M, Zhou BB, Hobson K, Scott S, Young D, Khanna KK . (2001). J Biol Chem 276: 17276–17280.

  • Gowen LC, Avrutskaya AV, Latour AM, Koller BH, Leadon SA . (1998). Science 281: 1009–1012.

  • Gudmundsdottir K, Lord CJ, Witt E, Tutt AN, Ashworth A . (2004). EMBO Rep 5: 989–993.

  • Hakem R, de la Pompa JL, Elia A, Potter J, Mak TW . (1997). Nat Genet 16: 298–302.

  • Harkin DP, Bean JM, Miklos D, Song YH, Truong VB, Englert C et al. (1999). Cell 97: 575–586.

  • Hartman AR, Ford JM . (2002). Nat Genet 32: 180–184.

  • Hartwell L . (1997). Nature 387: 855–857.

  • Hashizume R, Fukuda M, Maeda I, Nishikawa H, Oyake D, Yabuki Y et al. (2001). J Biol Chem 276: 14537–14540.

  • Hefferin ML, Tomkinson AE . (2005). DNA Repair (Amsterdam) 4: 639–648.

  • Hoeijmakers JH . (2001). Nature 411: 366–374.

  • Ira G, Pellicioli A, Balijja A, Wang X, Fiorani S, Carotenuto W et al. (2004). Nature 431: 1011–1017.

  • Jin Y, Xu XL, Yang MC, Wei F, Ayi TC, Bowcock AM et al. (1997). Proc Natl Acad Sci USA 94: 12075–12080.

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

  • Josse L, Harley ME, Pires IM, Hughes DA . (2006). Biochem J 393: 303–309.

  • Joukov V, Chen J, Fox EA, Green JB, Livingston DM . (2001). Proc Natl Acad Sci USA 98: 12078–12083.

  • Kaelin WG . (2005). Nat Rev Cancer 5: 689–698.

  • Kennedy RD, Quinn JE, Mullan PB, Johnston PG, Harkin DP . (2004). J Natl Cancer Inst 96: 1659–1668.

  • Kleiman FE, Wu-Baer F, Fonseca D, Kaneko S, Baer R, Manley JL . (2005). Genes Dev 19: 1227–1237.

  • Kojic M, Yang H, Kostrub CF, Pavletich NP, Holloman WK . (2003). Mol Cell 12: 1043–1049.

  • Kojic M, Zhou Q, Lisby M, Holloman WK . (2005). Mol Cell Biol 25: 2547–2557.

  • Kraakman-van der Zwet M, Overkamp WJ, van Lange RE, Essers J, van Duijn-Goedhart A, Wiggers I et al. (2002). Mol Cell Biol 22: 669–679.

  • Krogan NJ, Lam MH, Fillingham J, Keogh MC, Gebbia M, Li J et al. (2004). Mol Cell 16: 1027–1034.

  • Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J et al. (2001). Nature 409: 860–921.

  • Larminat F, Germanier M, Papouli E, Defais M . (2002). Oncogene 21: 5188–5192.

  • Lee H, Trainer AH, Friedman LS, Thistlethwaite FC, Evans MJ, Ponder BA et al. (1999). Mol Cell 4: 1–10.

  • Lee JS, Collins KM, Brown AL, Lee CH, Chung JH . (2000). Nature 404: 201–204.

  • Lee M, Daniels MJ, Venkitaraman AR . (2004). Oncogene 23: 865–872.

  • Le Page F, Randrianarison V, Marot D, Cabannes J, Perricaudet M, Feunteun J et al. (2000). Cancer Res 60: 5548–5552.

  • Li J, Zou C, Bai Y, Wazer DE, Band V, Gao Q . (2006). Oncogene 25: 1186–1194.

  • Lieber MR, Ma Y, Pannicke U, Schwarz K . (2003). Nat Rev Mol Cell Biol 4: 712–720.

  • Lin HR, Ting NS, Qin J, Lee WH . (2003). J Biol Chem 278: 35979–35987.

  • Lomonosov M, Anand S, Sangrithi M, Davies R, Venkitaraman AR . (2003). Genes Dev 17: 3017–3022.

  • Ludwig T, Chapman DL, Papaioannou VE, Efstratiadis A . (1997). Genes Dev 11: 1226–1241.

  • Ma JL, Kim EM, Haber JE, Lee SE . (2003). Mol Cell Biol 23: 8820–8828.

  • Marmorstein LY, Kinev AV, Chan GK, Bochar DA, Beniya H, Epstein JA et al. (2001). Cell 104: 247–257.

  • Marston NJ, Richards WJ, Hughes D, Bertwistle D, Marshall CJ, Ashworth A . (1999). Mol Cell Biol 19: 4633–4642.

  • McCabe N, Lord CJ, Tutt AN, Martin NM, Smith GC, Ashworth A . (2005). Cancer Biol Ther 4: 934–936.

  • McCabe N, Turner NC, Lord CJ, Kluzed K, Biakowska A, Swift S et al. (2006). Cancer Res (in press).

  • McCarthy EE, Celebi JT, Baer R, Ludwig T . (2003). Mol Cell Biol 23: 5056–5063.

  • Moynahan ME, Chiu JW, Koller BH, Jasin M . (1999). Mol Cell 4: 511–518.

  • Moynahan ME, Cui TY, Jasin M . (2001a). Cancer Res 61: 4842–4850.

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

  • Mullan PB, Quinn JE, Gilmore PM, McWilliams S, Andrews H, Gervin C et al. (2001). Oncogene 20: 6123–6131.

  • Okada S, Ouchi T . (2003). J Biol Chem 278: 2015–2020.

  • Ouchi T, Monteiro AN, August A, Aaronson SA, Hanafusa H . (1998). Proc Natl Acad Sci USA 95: 2302–2306.

  • Patel KJ, Vu VP, Lee H, Corcoran A, Thistlethwaite FC, Evans MJ et al. (1998). Mol Cell 1: 347–357.

  • Paull TT, Cortez D, Bowers B, Elledge SJ, Gellert M . (2001). Proc Natl Acad Sci USA 98: 6086–6091.

  • Pellegrini L, Yu DS, Lo T, Anand S, Lee M, Blundell TL et al. (2002). Nature 420: 287–293.

  • Rothkamm K, Kruger I, Thompson LH, Lobrich M . (2003). Mol Cell Biol 23: 5706–5715.

  • Ruffner H, Joazeiro CA, Hemmati D, Hunter T, Verma IM . (2001). Proc Natl Acad Sci USA 98: 5134–5139.

  • Saeki H, Siaud N, Christ N, Wiegant WW, van Buul PP, Han M et al. (2006). Proc Natl Acad Sci USA 103: 8768–8773.

  • Scully R, Chen J, Ochs RL, Keegan K, Hoekstra M, Feunteun J et al. (1997a). Cell 90: 425–435.

  • Scully R, Chen J, Plug A, Xiao Y, Weaver D, Feunteun J et al. (1997b). Cell 88: 265–275.

  • Sharan SK, Morimatsu M, Albrecht U, Lim DS, Regel E, Dinh C et al. (1997). Nature 386: 804–810.

  • Shen SX, Weaver Z, Xu X, Li C, Weinstein M, Chen L et al. (1998). Oncogene 17: 3115–3124.

  • Shin DS, Chahwan C, Huffman JL, Tainer JA . (2004). DNA Repair (Amsterdam) 3: 863–873.

  • Somasundaram K, Zhang H, Zeng YX, Houvras Y, Peng Y, Wu GS et al. (1997). Nature 389: 187–190.

  • Sone T, Saeki Y, Toh-e A, Yokosawa H . (2004). J Biol Chem 279: 28807–28816.

  • Spain BH, Larson CJ, Shihabuddin LS, Gage FH, Verma IM . (1999). Proc Natl Acad Sci USA 96: 13920–13925.

  • Starita LM, Horwitz AA, Keogh MC, Ishioka C, Parvin JD, Chiba N . (2005). J Biol Chem 280: 24498–24505.

  • Stark JM, Pierce AJ, Oh J, Pastink A, Jasin M . (2004). Mol Cell Biol 24: 9305–9316.

  • Takata M, Sasaki MS, Sonoda E, Morrison C, Hashimoto M, Utsumi H et al. (1998). EMBO J 17: 5497–5508.

  • Takata M, Tachiiri S, Fujimori A, Thompson LH, Miki Y, Hiraoka M et al. (2002). Oncogene 21: 1130–1134.

  • Tarsounas M, Davies D, West SC . (2003). Oncogene 22: 1115–1123.

  • Tibbetts RS, Cortez D, Brumbaugh KM, Scully R, Livingston D, Elledge SJ et al. (2000). Genes Dev 14: 2989–3002.

  • Turner N, Tutt A, Ashworth A . (2004). Nat Rev Cancer 4: 814–819.

  • Tutt A, Bertwistle D, Valentine J, Gabriel A, Swift S, Ross G et al. (2001). EMBO J 20: 4704–4716.

  • Tutt A, Gabriel A, Bertwistle D, Connor F, Paterson H, Peacock J et al. (1999). Curr Biol 9: 1107–1110.

  • Tutt A, Lord CJ, McCabe N, Farmer H, Turner N, Jackson SP et al. (2005). Molecular Approaches to Controlling Cancer: Cold Spring Harbour Symposia Quantitative Biology LXX. Stillman B, Stewart D (ed). CSHL Press: NY, pp. 139–148.

  • Valerie K, Povirk LF . (2003). Oncogene 22: 5792–5812.

  • van Gent DC, Hoeijmakers JH, Kanaar R . (2001). Nat Rev Genet 2: 196–206.

  • Wang HC, Chou WC, Shieh SY, Shen CY . (2006). Cancer Res 66: 1391–1400.

  • Wang Y, Cortez D, Yazdi P, Neff N, Elledge SJ, Qin J . (2000). Genes Dev 14: 927–939.

  • Warren M, Smith A, Partridge N, Masabanda J, Griffin D, Ashworth A . (2002). Hum Mol Genet 11: 841–851.

  • West SC . (2003). Nat Rev Mol Cell Biol 4: 435–445.

  • Westermark UK, Reyngold M, Olshen AB, Baer R, Jasin M, Moynahan ME . (2003). Mol Cell Biol 23: 7926–7936.

  • Williamson EA, Dadmanesh F, Koeffler HP . (2002). Oncogene 21: 3199–3206.

  • Wong AK, Pero R, Ormonde PA, Tavtigian SV, Bartel PL . (1997). J Biol Chem 272: 31941–31944.

  • Wu LC, Wang ZW, Tsan JT, Spillman MA, Phung A, Xu XL et al. (1996). Nat Genet 14: 430–440.

  • Xu B, Kim S, Kastan MB . (2001a). Mol Cell Biol 21: 3445–3450.

  • Xu B, O'Donnell AH, Kim ST, Kastan MB . (2002). Cancer Res 62: 4588–4591.

  • Xu X, Qiao W, Linke SP, Cao L, Li WM, Furth PA . (2001b). Nat Genet 28: 266–271.

  • Xu X, Weaver Z, Linke SP, Li C, Gotay J, Wang XW et al. (1999). Mol Cell 3: 389–395.

  • Yang H, Jeffrey PD, Miller J, Kinnucan E, Sun Y, Thoma NH et al. (2002). Science 297: 1837–1848.

  • Yang H, Li Q, Fan J, Holloman WK, Pavletich NP . (2005). Nature 433: 653–657.

  • Yarden RI, Pardo-Reoyo S, Sgagias M, Cowan KH, Brody LC . (2002). Nat Genet 30: 285–289.

  • Yu DS, Sonoda E, Takeda S, Huang CL, Pellegrini L, Blundell TL et al. (2003). Mol Cell 12: 1029–1041.

  • Yu VP, Koehler M, Steinlein C, Schmid M, Hanakahi LA, van Gool AJ et al. (2000). Genes Dev 14: 1400–1406.

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

  • Zhang H, Somasundaram K, Peng Y, Tian H, Bi D, Weber B et al. (1998). Oncogene 16: 1713–1721.

  • Zhang J, Willers H, Feng Z, Ghosh JC, Kim S, Weaver DT et al. (2004). Mol Cell Biol 24: 708–718.

  • Zhong Q, Boyer TG, Chen PL, Lee WH . (2002). Cancer Res 62: 3966–3970.

  • Zhong Q, Chen CF, Li S, Chen Y, Wang CC, Xiao J et al. (1999). Science 285: 747–750.

  • Zhuang J, Zhang J, Willers H, Wang H, Chung JH, van Gent DC et al. (2006). Cancer Res 66: 1401–1408.

Download references

Acknowledgements

We are grateful to the members of the Ashworth laboratory for useful comments during the writing of this review, with special thanks to Nuala McCabe. Work in our laboratory is funded by Breakthrough Breast Cancer and Cancer Research UK.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to A Ashworth.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gudmundsdottir, K., Ashworth, A. The roles of BRCA1 and BRCA2 and associated proteins in the maintenance of genomic stability. Oncogene 25, 5864–5874 (2006). https://doi.org/10.1038/sj.onc.1209874

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1209874

Keywords

This article is cited by

Search

Quick links