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Homologous repair of DNA damage and tumorigenesis:the BRCA connection

Abstract

Homologous recombination has been recognized in recent years to be an important DNA repair pathway in mammalian cells, for such damage as chromosomal double-strand breaks. Cells mutated for the genes involved in the hereditary breast and ovarian cancer susceptibility syndromes, i.e. BRCA1 and BRCA2, show defects in DNA repair by homologous recombination, implicating this repair pathway in protecting individuals against tumorigenesis. This review summarizes recent advances in our understanding of BRCA1 and BRCA2 in DNA repair, as well as insight into these proteins gleaned from structure determination of domains of these proteins and the broader evolutionary conservation than previously appreciated.

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References

  • Baldeyron C, Jacquemin E, Smith J, Jacquemont C, De Oliveira I, Gad S, Feunteun J, Stoppa-Lyonnet D, Papadopoulo D . 2002 Oncogene 21: 1401–1410

  • Bassing CH, Chua KF, Sekiguchi J, Suh H, Whitlow SR, Fleming JC, Monroe BC, Ciccone DN, Yan C, Vlasakova K, Livingston DM, Ferguson DO, Scully R, Alt FW . 2002 Proc. Natl. Acad. Sci. USA 99: 8173–8178

  • Baumann P, Benson FE, West SC . 1996 Cell 87: 757–766

  • Baumann P, West SC . 1997 EMBO J. 16: 5198–5206

  • Baumann P, West SC . 1998 Proc. Natl. Acad. Sci. USA 95: 14066–14070

  • Begg CB . 2002 J. Natl. Cancer Inst. 94: 1221–1226

  • 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

  • Bork P, Blomberg N, Nilges M . 1996 Nat. Genet. 13: 22–23

  • Brzovic PS, Meza JE, King MC, Klevit RE . 2001a J. Biol. Chem. 276: 41399–41406

  • Brzovic PS, Rajagopal P, Hoyt DW, King MC, Klevit RE . 2001b Nat. Struct. Biol. 8: 833–837

  • Callebaut I, Mornon JP . 1997 FEBS Lett. 400: 25–30

  • Caspari T, Murray JM, Carr AM . 2002 Genes Dev. 16: 1195–1208

  • Celeste A, Petersen S, Romanienko PJ, Fernandez-Capetillo O, Chen HT, Sedelnikova OA, Reina-San-Martin B, Coppola V, Meffre E, Difilippantonio MJ, Redon C, Pilch DR, Olaru A, Eckhaus M, Camerini-Otero RD, Tessarollo L, Livak F, Manova K, Bonner WM, Nussenzweig MC, Nussenzweig A . 2002 Science 296: 922–927

  • Chandler J, Hohenstein P, Swing DA, Tessarollo L, Sharan SK . 2001 Genesis 29: 72–77

  • Chen A, Kleiman FE, Manley JL, Ouchi T, Pan ZQ . 2002 J. Biol. Chem. 277: 22085–22092

  • Chen CF, Chen PL, Zhong Q, Sharp ZD, Lee WH . 1999 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, Scully R . 1998a Mol. Cell. 2: 317–328

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

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

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

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

  • Cressman VL, Backlund DC, Avrutskaya AV, Leadon SA, Godfrey V, Koller BH . 1999 Mol. Cell. Biol. 19: 7061–7075

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

  • Fabbro M, Rodriguez JA, Baer R, Henderson BR . 2002 J. Biol. Chem. 277: 21315–21324

  • Feldmann E, Schmiemann V, Goedecke W, Reichenberger S, Pfeiffer P . 2000 Nucleic Acids Res. 28: 2585–2596

  • Ganesan S, Silver DP, Greenberg RA, Avni D, Drapkin R, Miron A, Mok SC, Randrianarison V, Brodie S, Salstrom J, Rasmussen TP, Klimke A, Marrese C, Marahrens Y, Chu-Xia Deng CX, Feunteun J, Livingston DM . 2002 Cell 111: 393–405

  • Garcia-Higuera I, Taniguchi T, Ganesan S, Meyn MS, Timmers C, Hejna J, Grompe M, d'Andrea AD . 2001 Mol. Cell. 7: 249–262

  • Gasior SL, Olivares H, Ear U, Hari DM, Weichselbaum R, Bishop DK . 2001 Proc. Natl. Acad. Sci. USA 98: 8411–8488

  • Gatei M, Scott SP, Filipovitch I, Soronika N, Lavin MF, Weber B, Khanna KK . 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

  • Goggins M, Schutte M, Lu J, Moskaluk CA, Weinstein CL, Petersen GM, Yeo CJ, Jackson CE, Lynch HT, Hruban RH, Kern SE . 1996 Cancer Res. 56: 5360–5364

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

  • Gowen LC, Johnson BL, Latour AM, Sulik KK, Koller BH . 1996 Nat. Genet. 12: 191–194

  • Haber JE . 1998 Cell 95: 583–586

  • 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, Mak TW . 1996 Cell 85: 1009–1023

  • Hashizume R, Fukuda M, Maeda I, Nishikawa H, Oyake D, Yabuki Y, Ogata H, Ohta T . 2001 J. Biol. Chem. 276: 14537–14540

  • Huber LJ, Yang TW, Sarkisian CJ, Master SR, Deng CX, Chodosh LA . 2001 Mol. Cell Biol. 21: 4005–4015

  • Jasin M . 2001 DNA Damage and Repair Vol. III: Nickoloff JA & Hoekstra, M.F. (eds) Totowa, N.J.: Humana Press pp. 207–235

    Book  Google Scholar 

  • Jensen DE, Proctor M, Marquis ST, Gardner HP, Ha SI, Chodosh LA, Ishov AM, Tommerup N, Vissing H, Sekido Y, Minna J, Borodovsky A, Schultz DC, Wilkinson KD, Maul GG, Barlev N, Berger SL, Prendergast GC, Rauscher 3rd FJ . 1998 Oncogene 16: 1097–1112

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

  • Johnson RD, Jasin M . 2001 Biochem. Soc. Trans. 29: 196–201

  • Joo WS, Jeffrey PD, Cantor SB, Finnin MS, Livingston DM, Pavletich NP . 2002 Genes Dev. 16: 583–593

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

  • Kojic M, Kostrub CF, Buchman AR, Holloman WK . 2002 Mol. Cell. 10: 683–691

  • Koonin EV, Altschul SF, Bork P . 1996 Nat. Genet. 13: 266–268

  • 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

  • Lane TF, Lin C, Brown MA, Solomon E, Leder P . 2000 Oncogene 19: 4085–4090

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

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

  • Lorick KL, Jensen JP, Fang S, Ong AM, Hatakeyama S, Weissman AM . 1999 Proc. Natl. Acad. Sci. USA 96: 11364–11369

  • Lovering R, Hanson IM, Borden KL, Martin S, O'Reilly NJ, Evan GI, Rahman D, Pappin DJ, Trowsdale J, Freemont PS . 1993 Proc. Natl. Acad. Sci. USA 90: 2112–2116

  • Ludwig T, Fisher P, Ganesan S, Efstratiadis A . 2001 Genes Dev. 15: 1188–1193

  • Mak TW, Hakem A, McPherson JP, Shehabeldin A, Zablocki E, Migon E, Duncan GS, Bouchard D, Wakeham A, Cheung A, Karaskova J, Sarosi I, Squire J, Marth J, Hakem R . 2000 Nat. Immunol. 1: 77–82

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

  • McAllister KA, Bennett LM, Houle CD, Ward T, Malphurs J, Collins NK, Cachafeiro C, Haseman J, Goulding EH, Bunch D, Eddy EM, Davis BJ, Wiseman RW . 2002 Cancer Res. 62: 990–994

  • McAllister KA, Haugen-Strano A, Hagevik S, Brownlee HA, Collins NK, Futreal PA, Bennett LM, Wiseman RW . 1997 Cancer Res. 57: 3121–3125

  • Mérel P, Prieur A, Pfeiffer P, Delattre O . 2002 Oncogene 21: 5654–5659

  • Meza JE, Brzovic PS, King MC, Klevit RE . 1999 J. Biol. Chem. 274: 5659–5665

  • Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, Liu Q, Cochran C, Bennett LM, Ding W . et al. 1994 Science 266: 66–71

  • Mizuta R, LaSalle JM, Cheng HL, Shinohara A, Ogawa H, Copeland N, Jenkins NA, Lalande M, Alt FW . 1997 Proc. Natl. Acad. Sci. USA 94: 6927–6932

  • Monteiro AN . 2000 Trends Biochem. Sci. 25: 469–474

  • Morimatsu M, Donoho G, Hasty P . 1998 Cancer Res. 58: 3441–3447

  • Moynahan ME . 2002 Oncogene Rev., in press

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

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

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

  • Orelli BJ, Logsdon Jr JM, Bishop DK . 2001 Oncogene 20: 4433–4438

  • Pâques F, Haber JE . 1999 Microbiol. Mol. Biol. Rev. 63: 349–404

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

  • Paull TT . 2001 Cell 107: 563–565

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

  • Paull TT, Rogakou EP, Yamazaki V, Kirchgessner CU, Gellert M, Bonner WM . 2000 Curr. Biol. 10: 886–895

  • Pellegrini L, Yu DS, Lo T, Anand S, Lee MY, Blundell TL, Venkitaraman AR . 2002 Nature, 420: 287–293

  • Pierce AJ, Stark J, Araujo FD, Moynahan ME, Berwick M, Jasin M . 2001 Trends Cell Biol. 11: S52–S59

  • Rodriguez JA, Henderson BR . 2000 J. Biol. Chem. 275: 38589–38596

  • Rouet P, Smih F, Jasin M . 1994 Mol. Cell. Biol. 14: 8096–8106

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

  • Ruffner H, Verma IM . 1997 Proc. Natl. Acad. Sci. USA 94: 7138–7143

  • Sarkisian CJ, Master SR, Huber LJ, Ha SI, Chodosh LA . 2001 J. Biol. Chem. 276: 37640–37648

  • Scully R, Chen J, Ochs RL, Keegan K, Hoekstra M, Feunteun J, Livingston DM . 1997a Cell 90: 425–435

  • Scully R, Chen J, Plug A, Xiao Y, Weaver D, Feunteun J, Ashley T, Livingston DM . 1997b Cell 88: 265–275

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

  • Scully R, Livingston DM . 2000 Nature 408: 429–432

  • Sharan SK, Bradley A . 1997 Genomics 40: 234–241

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

  • Shen SX, Weaver Z, Xu X, Li C, Weinstein M, Chen L, Guan XY, Ried T, Deng CX . 1998 Oncogene 17: 3115–3124

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

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

  • Stark JM, Hu P, Pierce AJ, Moynahan ME, Ellis N, Jasin M . 2002 J. Biol. Chem. 277: 20185–20194

  • 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, Mak TW . 1997 Genes Dev. 11: 1242–1252

  • Takata M, Tachiiri S, Fujimori A, Thompson LH, Miki Y, Hiraoka M, Takeda S, Yamazoe M . 2002 Oncogene 21: 1130–1134

  • 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, Goldgar DE et al . 1996 Nat. Genet. 12: 333–337

  • Thai TH, Du F, Tsan JT, Jin Y, Phung A, Spillman MA, Massa HF, Muller CY, Ashfaq R, Mathis JM, Miller DS, Trask BJ, Baer R, Bowcock AM . 1998 Hum. Mol. Genet. 7: 195–202

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

  • Tirkkonen M, Johannsson O, Agnarsson BA, Olsson H, Ingvarsson S, Karhu R, Tanner M, Isola J, Barkardottir RB, Borg A, Kallioniemi OP . 1997 Cancer Res. 57: 1222–1227

  • Turner BC, Ottey M, Zimonjic DB, Potoczek M, Hauck WW, Pequignot E, Keck-Waggoner CL, Sevikgnani C, Aldaz CM, McCue PA, Palazzo J, Huebner K, Popescu NC . 2002 Cancer Res. 62: 4054–4060

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

  • Tutt AN, van Oostrom CT, Ross GM, van Steeg H, Ashworth A . 2002 EMBO Rep. 3: 255–260

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

  • Vogelstein B, Kinzler KW . (eds) 1998 The genetic basis of human cancer McGraw-Hill, New York

    Google Scholar 

  • Wang B, Matsuoka S, Carpenter PB, Elledge SJ . 2002 Science 298: 1435–1438

  • Wang H, Zeng ZC, Bui TA, DiBiase SJ, Qin W, Xia F, Powell SN, Iliakis G . 2001 Cancer Res. 61: 270–277

  • 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

  • Welcsh PL, King MC . 2001 Hum. Mol. Genet. 10: 705–713

  • Welcsh PL, Owens KN, King MC . 2000 Trends Genet. 16: 69–74

  • Williams RS, Green R, Glover JN . 2001 Nat. Struct. Biol. 8: 838–842

  • Wong AKC, 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, Yang MC, Hwang LY, Bowcock AM, Baer R . 1996 Nat. Genet. 14: 430–440

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

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

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

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

  • Yamane K, Katayama E, Tsuruo T . 2000 Biochem. Biophys. Res. Commun. 279: 678–684

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

  • Yano K, Morotomi K, Saito H, Kato M, Matsuo F, Miki Y . 2000 Biochem. Biophys. Res. Commun. 270: 171–175

  • Ye Q, Hu YF, Zhong H, Nye AC, Belmont AS, Li R . 2001 J. Cell Biol. Biol. 155: 911–921

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

  • Yu X, Baer R . 2000 J. Biol. Chem. 275: 18541–18549

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

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

  • Zhong Q, Chen CF, Chen PL, Lee WH . 2002b J. Biol. Chem. 277: 28641–28647

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

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Acknowledgements

We thank Richard Baer and Nicole Christ for comments on the manuscript and Larry Norton for support through the Wolfson Family Foundation, the Breast Cancer Research Fund, and NIH P01CA94060.

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Jasin, M. Homologous repair of DNA damage and tumorigenesis:the BRCA connection. Oncogene 21, 8981–8993 (2002). https://doi.org/10.1038/sj.onc.1206176

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