[go: up one dir, main page]
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:

Roles of BRCA1 and BRCA2 in homologous recombination, DNA replication fidelity and the cellular response to ionizing radiation

Oncogene volume 22, pages 5784–5791 (2003)Cite this article

Abstract

Inheritance of one defective copy of either of the two breast cancer susceptibility genes, BRCA1 and BRCA2, predisposes individuals to breast and ovarian cancers. Current progress in determining the function of these genes suggests that they participate in a common pathway to facilitate orderly homologous recombination and thereby maintain genomic integrity. As a consequence of this defect in homologous recombination, tumors that arise in BRCA carriers are likely to be more sensitive to ionizing radiation. This review summarizes recent investigations about the nature of the defect in DNA repair, and highlights the unanswered questions about the tumor suppressor paradox of BRCA genes. The unsolved mystery is the other genetic changes that must occur to turn a BRCA-deficient cell from a nonviable cell into a tumor cell capable of endless growth.

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

Access options

Buy this article

  • Purchase on SpringerLink
  • 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

  • Anderson SF, Schlegel BP, Nakajima T, Wolpin ES and Parvin JD . (1998). Nat. Genet., 19, 254–256.

  • Baer R and Ludwig T . (2002). Curr. Opin. Genet. Dev., 12, 86–91.

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

  • Chen CF, Chen PL, Zhong Q, Sharp ZD and Lee WH . (1999a). J. Biol. Chem., 274, 32931–32935.

  • Chen J, Silver DP, Walpita D, Cantor SB, Gazdar AF, Tomlinson G, Couch FJ, Weber BL, Ashley T, Livingston DM and Scully R . (1998a). Mol. Cell, 2, 317–328.

  • Chen JJ, Silver D, Cantor S, Livingston DM and Scully R . (1999b). Cancer Res., 59, 1752s–1756s.

  • Chen PL, Chen CF, Chen Y, Xiao J, Sharp ZD and Lee WH . (1998b). Proc. Natl. Acad. Sci. USA, 95, 5287–5292.

  • Crook T, Brooks LA, Crossland S, Osin P, Barker KT, Waller J, Philp E, Smith PD, Yulug I, Peto J, Parker G, Allday MJ, Crompton MR and Gusterson BA . (1998). Oncogene, 17, 1681–1689.

  • Crook T, Crossland S, Crompton MR, Osin P and Gusterson BA . (1997). Lancet, 350, 638–639.

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

  • Deng CX and Brodie SG . (2000). BioEssays, 22, 728–737.

  • DiBiase SJ, Zeng ZC, Chen R, Hyslop T, Curran Jr WJ and Iliakis G . (2000). Cancer Res., 60, 1245–1253.

  • Ford D, Easton DF, Bishop DT, Narod SA and Goldgar DE . (1994). Lancet, 343, 692–695.

  • Ford D, Easton DF, Stratton M, Narod S, Goldgar D, Devilee P, Bishop DT, Weber B, Lenoir G, Chang-Claude J, Sobol H, Teare MD, Struewing J, Arason A, Scherneck S, Peto J, Rebbeck TR, Tonin P, Neuhausen S, Barkardottir R, Eyfjord J, Lynch H, Ponder BA, Gayther SA, Birch JM, Lindblom A, Stoppa-Lyonnet D, Bignon Y, Borg A, Hamann U, Haites N, Scott RJ, Maugard CM, Vasen H, Seitz S, Cannon-Albright LA, Schofield A, Zelada-Hedman M and the Breast Cancer Linkage Consortium. (1998). Am. J. Hum. Genet., 62, 676–689.

  • Futamura M, Arakawa H, Matsuda K, Katagiri T, Saji S, Miki Y and Nakamura Y . (1531). Cancer Res., 60, 1531–1535.

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

  • Goodman MF . (2000). Trends Biochem. Sci., 25, 189–195.

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

  • Haber JE and Heyer WD . (2001). Cell, 107, 551–554.

  • Haile DT and Parvin JD . (1999). J. Biol. Chem., 274, 2113–2117.

  • Hakem R, de la Pompa JL and Mak TW . (1998). J. Mammary Gland Biol. Neoplasia, 3, 431–445.

  • Hakem R, de la Pompa JL, Sirard C, Mo R, Woo M, Hakem A, Wakeham A, Potter J, Reitmair A, Billia F, Firpo E, Hui CC, Roberts J, Rossant J and Mak TW . (1996). Cell, 85, 1009–1023.

  • Hall JM, Lee MK, Newman B, Morrow JE, Anderson LA, Huey B and King MC . (1990). Science, 250, 1684–1689.

  • Harkin DP, Bean JM, Miklos D, Song YH, Truong VB, Englert C, Christians FC, Ellisen LW, Maheswaran S, Oliner JD and Haber DA . (1999). Cell, 97, 575–586.

  • Hofmann W and Schlag PM . (2000). J. Cancer Res. Clin. Oncol., 126, 487–496.

  • Jacks T and Weinberg RA . (1998). Science, 280, 1035–1036.

  • Kinzler KW and Vogelstein B . (1997). Nature, 386, 761–763.

  • 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 and Zdzienicka MZ . (2002). Mol. Cell. Biol., 22, 669–679.

  • Lakhani SR, Gusterson BA, Jacquemier J, Sloane JP, Anderson TJ, van de Vijver MJ, Venter D, Freeman A, Antoniou A, McGuffog L, Smyth E, Steel CM, Haites N, Scott RJ, Goldgar D, Neuhausen S, Daly PA, Ormiston W, McManus R, Scherneck S, Ponder BA, Futreal PA, Peto J, Stoppa-Lyonnet D, Bignon YJ and Stratton MR . (2000). Clin. Cancer Res., 6, 782–789.

  • Lakhani SR, Jacquemier J, Sloane JP, Gusterson BA, Anderson TJ, van de Vijver MJ, Farid LM, Venter D, Antoniou A, Storfer-Isser A, Smyth E, Steel CM, Haites N, Scott RJ, Goldgar D, Neuhausen S, Daly PA, Ormiston W, McManus R, Scherneck S, Ponder BA, Ford D, Peto J, Stoppa-Lyonnet D, Bignon YJ, Struewing JP, Spurr NK, Bishop DT, Klijn JGM, Devilee P, Cornelisse CJ, Lasset C, Lenoir G, Barkardottir RB, Egilsson VHU, Chang-Claude J, Sobol H, Weber B, Stratton MR and Easton DF . (1998). J. Natl. Cancer Inst., 90, 1138–1145.

  • Lakhani SR, Van De Vijver MJ, Jacquemier J, Anderson TJ, Osin PP, McGuffog L and Easton DF . (2002). J. Clin. Oncol., 20, 2310–2318.

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

  • Lehmann AR, Arlett CF, Burke JF, Green MH, James MR and Lowe JE . (1986). Int. J. Radiat. Biol., 49, 639–643.

  • Li S, Chen PL, Subramanian T, Chinnadurai G, Tomlinson G, Osborne CK, Sharp ZD and Lee WH . (1999). J. Biol. Chem., 274, 11334–11338.

  • MacLachlan TK, Somasundaram K, Sgagias M, Shifman Y, Muschel RJ, Cowan KH and El-Deiry WS . (2000). Journal of Biological Chemistry, 275, 2777–2785.

  • Marmorstein LY, Kinev AV, Chan GK, Bochar DA, Beniya H, Epstein JA, Yen TJ and Shiekhattar R . (2001). Cell, 104, 247–257.

  • Miki Y, Swensen J, Shattuck-Eidens D, Futreal AP, Harshman K, Tavtigian S, Liu Q, Cochran C, Bennett ML, Wei D, Russell B, Rosenthal J, Hussey C, Tran T, McClure M, Frye C, Hattier T, Phelps R, Haugen-Strano A, Katcher H, Yakumo K, Gholami Z, Shaffer D, Stone S, Bayer S, Wray C, Bogden R, Dayananth P, Ward J, Tonin P, Narod S, Bristow PK, Norris FH, Helvering L, Morrison P, Rosteck P, Lai M, Barrett JC, Lewis C, Neuhausen S, Cannon-Albright L, Goldgar D, Wiseman R, Kamb A and Skolnick MH . (1994). Science, 266, 66–71.

  • Milner J, Fuks F, Hughes-Davies L and Kouzarides T . (2000). Oncogene, 19, 4441–4445.

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

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

  • Paakkonen K, Sauramo S, Sarantaus L, Vahteristo P, Hartikainen A, Vehmanen P, Ignatius J, Ollikainen V, Kaariainen H, Vauramo E, Nevanlinna H, Krahe R, Holli K and Kere J . (2001). Genet. Epidemiol., 20, 239–246.

  • Parvin JD . (2001). Proc. Natl. Acad. Sci. USA, 98, 5952–5954.

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

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

  • Pellegrini L, Yu DS, Lo T, Anand S, Lee M, Blundell TL and Venkitaraman AR . (2002). Nature, 420, 287–293.

  • Peto J, Collins N, Barfoot R, Seal S, Warren W, Rahman N, Easton DF, Evans C, Deacon J and Stratton MR . (1999). J. Natl. Cancer Inst., 91, 943–949.

  • Powell SN, Willers H and Xia F . (2002). Mol. Cell, 10, 1262–1263.

  • Satagopan JM, Offit K, Foulkes W, Robson ME, Wacholder S, Eng CM, Karp SE and Begg CB . (2001). Cancer Epidemiol. Biomarkers Prev., 10, 467–473.

  • Schlegel BP, Green VJ, Ladias JA and Parvin JD . (2000). Proc. Natl. Acad. Sci. USA, 97, 3148–3153.

  • Schubert EL, Lee MK, Mefford HC, Argonza RH, Morrow JE, Hull J, Dann JL and King MC . (1997). Am. J. Hum. Genet., 60, 1031–1040.

  • Scully R, Anderson SF, Chao DM, Wei W, Ye L, Young RA, Livingston DM and Parvin JD . (1997). Proc. Natl. Acad. Sci. USA, 94, 5605–5610.

  • Scully R, Ganesan S, Vlasakova K, Chen J, Socolovsky M and Livingston DM . (1999). Mol. Cell, 4, 1093–1099.

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

  • Smith PD, Crossland S, Parker G, Osin P, Brooks L, Waller J, Philp E, Crompton MR, Gusterson BA, Allday MJ and Crook T . (1999a). Oncogene, 18, 2451–2459.

  • Smith PD, Crossland S, Parker G, Osin P, Brooks L, Waller J, Philp E, Crompton MR, Gusterson BA, Allday MJ and Crook T . (1999b). Oncogene, 18, 2451–2459.

  • Snouwaert JN, Gowen LC, Latour AM, Mohn AR, Xiao A, DiBiase L and Koller BH . (1999). Oncogene, 18, 7900–7907.

  • Somasundaram K, MacLachlan TK, Burns TF, Sgagias M, Cowan KH, Weber BL and el-Deiry WS . (1999). Oncogene, 18, 6605–6614.

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

  • Suzuki A, de la Pompa JL, Hakem R, Elia A, Yoshida R, Mo R, Nishina H, Chuang T, Wakeham A, Itie A, Koo W, Billia P, Ho A, Fukumoto M, Hui CC and Mak TW . (1997). Genes Dev., 11, 1242–1252.

  • Taghian DG and Nickoloff JA . (1997). Mol. Cell. Biol., 17, 6386–6393.

  • Thangaraju M, Kaufmann SH and Couch FJ . (2000). J. Biol. Chem., 275, 33487–33496.

  • Tibbetts RS, Cortez D, Brumbaugh KM, Scully R, Livingston D, Elledge SJ and Abraham RT . (2000). Genes Dev., 14, 2989–3002.

  • Tutt A, Bertwistle D, Valentine J, Gabriel A, Swift S, Ross G, Griffin C, Thacker J and Ashworth A . (2001). EMBO J., 20, 4704–4716.

  • Wang H, Zeng Z, Bui T, DiBiase S, Qin W, Xia F, Powell S and Iliakis G . (2001). Cancer Res., 61, 270–277.

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

  • Wilson CA, Ramos L, Villasenor MR, Anders KH, Press MF, Clarke K, Karlan B, Chen JJ, Scully R, Livingston D, Zuch RH, Kanter MH, Cohen S, Calzone FJ and Slamon DJ . (1999). Nat. Genet., 21, 236–240.

  • Wooster R, Bignell G, Lancaster J, Swift S, Seal S, Mangion J, Collins N, Gregory S, Gumbs C and Micklem G . (1995). Nature, 378, 789–792.

  • Wu X, Petrini JH, Heine WF, Weaver DT, Livingston DM and Chen J . (2000). Science, 289, 11.

  • Xia F, Taghian DG, DeFrank JS, Zeng ZC, Willers H, Iliakis G and Powell SN . (2001). Proc. Natl. Acad. Sci. USA, 98, 8644–8649.

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

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

  • Xu X, Wagner KU, Larson D, Weaver Z, Li C, Ried T, Hennighausen L, Wynshaw-Boris A and Deng CX . (1999a). Nat. Genet., 22, 37–43.

  • Xu X, Weaver Z, Linke SP, Li C, Gotay J, Wang XW, Harris CC, Ried T and Deng CX . (1999b). Mol. Cell, 3, 389–395.

  • Yang H, Jeffrey PD, Miller J, Kinnucan E, Sun Y, Thoma NH, Zheng N, Chen PL, Lee WH and Pavletich NP . (2002). Science, 297, 1837–1848.

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

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

  • Zhong Q, Chen CF, Li S, Chen Y, Wang CC, Xiao J, Chen PL, Sharp ZD and Lee WH . (1999). Science, 285, 747–750.

Download references

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA

    Simon N Powell

  2. Department of Radiation Oncology, Boston Medical Center, Boston, MA, USA

    Lisa A Kachnic

Authors
  1. Simon N Powell
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lisa A Kachnic
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Simon N Powell.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Powell, S., Kachnic, L. Roles of BRCA1 and BRCA2 in homologous recombination, DNA replication fidelity and the cellular response to ionizing radiation. Oncogene 22, 5784–5791 (2003). https://doi.org/10.1038/sj.onc.1206678

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1206678

Keywords

This article is cited by

Search

Advanced search

Quick links