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The role of BRCA1 in transcriptional regulation and cell cycle control

Abstract

The exact functions of BRCA1 have not been fully described but it now seems apparent that it has roles in DNA damage repair, transcriptional regulation, cell cycle control and most recently in ubiquitylation. These functions of BRCA1 are most likely interdependent but this review will focus on the role of BRCA1 in relation to transcriptional regulation and in particular how this impacts upon cell cycle control. We will (i) describe the structure of BRCA1 and how it may contribute to its transcription function; (ii) describe the interaction of BRCA1 with the core transcriptional machinery (RNA polII); (iii) describe how BRCA1 may regulate transcription at an epigenetic level through chromatin modification; (iv) discuss the role of BRCA1 in modulating transcription through its association with sequence-specific transcription factors. Finally, we will discuss the possible effects of BRCA1 transcriptional regulation on downstream targets with known roles in cell cycle control.

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References

  • Ahmad N, Cheng P, Mukhtar H . (2000). Biochem Biophys Res Commun 275: 328–334.

  • Aiyar SE, Sun JL, Blair AL, Moskaluk CA, Lu YZ, Ye QN et al. (2004). Genes Dev 18: 2134–2146.

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

  • Andrews HN, Mullan PB, McWilliams S, Sebelova S, Quinn JE, Gilmore PM et al. (2002). J Biol Chem 277: 26225–26232.

  • Aprelikova O, Pace AJ, Fang B, Koller BH, Liu ET . (2001). J Biol Chem 276: 25647–25650.

  • Bernabei P, Bosticardo M, Losana G, Regis G, Di Paola F, De Angelis S et al. (2003). Blood 102: 2933–2939.

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

  • Bork P, Hofmann K, Bucher P, Neuwald AF, Altschul SF, Koonin EV . (1997). FASEB J 11: 68–76.

  • Cabart P, Chew HK, Murphy S . (2004). Oncogene 23: 5316–5329.

  • Chai YL, Cui J, Shao N, Shyam E, Reddy P, Rao VN . (1999). Oncogene 18: 263–268.

  • Chappuis PO, Kapusta L, Begin LR, Wong N, Brunet JS, Narod SA et al. (2000). J Clin Oncol 18: 4045–4052.

  • Chen GC, Guan LS, Yu JH, Li GC, Choi Kim HR, Wang ZY . (2001). Biochem Biophys Res Commun 284: 507–514.

  • Chen Y, Farmer AA, Chen CF, Jones DC, Chen PL, Lee WH . (1996). Cancer Res 56: 3168–3172.

  • Chiba N, Parvin JD . (2002). Cancer Res 62: 4222–4228.

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

  • Fan S, Ma YX, Wang C, Yuan RQ, Meng Q, Wang JA et al. (2001). Oncogene 20: 77–87.

  • Fan S, Ma YX, Wang C, Yuan RQ, Meng Q, Wang JA et al. (2002a). Cancer Res 62: 141–151.

  • Fan S, Wang J, Yuan R, Ma Y, Meng Q, Erdos MR et al. (1999). Science 284: 1354–1356.

  • Fan W, Jin S, Tong T, Zhao H, Fan F, Antinore MJ et al. (2002b). J Biol Chem 277: 8061–8067.

  • Feng Z, Kachnic L, Zhang J, Powell SN, Xia F . (2004). J Biol Chem 279: 28574–28584.

  • Gilmore PM, McCabe N, Quinn JE, Kennedy RD, Gorski JJ, Andrews HN et al. (2004). Cancer Res 64: 4148–4154.

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

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

  • Hulka BS, Moorman PG . (2001). Maturitas 38: 103–113; discussion 113–116.

  • Humphrey JS, Salim A, Erdos MR, Collins FS, Brody LC, Klausner RD . (1997). Proc Natl Acad Sci USA 94: 5820–5825.

  • Ikeda T, Sato K, Kuwada N, Matsumura T, Yamashita T, Kimura F et al. (2002). J Leukoc Biol 72: 1198–1205.

  • Jin S, Zhao H, Fan F, Blanck P, Fan W, Colchagie AB et al. (2000). Oncogene 19: 4050–4057.

  • Kadam S, McAlpine GS, Phelan ML, Kingston RE, Jones KA, Emerson BM . (2000). Genes Dev 14: 2441–2451.

  • Kawai H, Li H, Chun P, Avraham S, Avraham HK . (2002). Oncogene 21: 7730–7739.

  • Kennedy RD, Gorski JJ, Quinn JE, Stewart GE, James CR, Moore S et al. (2005). Cancer Res 65: 10265–10272.

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

  • Krum SA, Miranda GA, Lin C, Lane TF . (2003). J Biol Chem 278: 52012–52020.

  • Li H, Lee TH, Avraham H . (2002). J Biol Chem 277: 20965–20973.

  • Li S, Chen PL, Subramanian T, Chinnadurai G, Tomlinson G, Osborne CK et al. (1999). J Biol Chem 274: 11334–11338.

  • Li S, Ting NS, Zheng L, Chen PL, Ziv Y, Shiloh Y et al. (2000). Nature 406: 210–215.

  • MacLachlan TK, Dash BC, Dicker DT, El-Deiry WS . (2000a). J Biol Chem 275: 31869–31875.

  • MacLachlan TK, Somasundaram K, Sgagias M, Shifman Y, Muschel RJ, Cowan KH et al. (2000b). J Biol Chem 275: 2777–2785.

  • MacLachlan TK, Takimoto R, El-Deiry WS . (2002). Mol Cell Biol 22: 4280–4292.

  • Manke IA, Lowery DM, Nguyen A, Yaffe MB . (2003). Science 302: 636–639.

  • Marie I, Durbin JE, Levy DE . (1998). EMBO J 17: 6660–6669.

  • Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S et al. (1994). Science 266: 66–71.

  • Moisan A, Larochelle C, Guillemette B, Gaudreau L . (2004). Mol Cell Biol 24: 6947–6956.

  • Monteiro AN, August A, Hanafusa H . (1996). Proc Natl Acad Sci USA 93: 13595–13599.

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

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

  • Mullan PB, Hosey AM, Buckley NE, Quinn JE, Kennedy RD, Johnston PG et al. (2005). Oncogene 24: 5492–5501.

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

  • Ogryzko VV, Wong P, Howard BH . (1997). Mol Cell Biol 17: 4877–4882.

  • Oishi H, Kitagawa H, Wada O, Takezawa S, Tora L, Kouzu-Fujita M et al. (2006). J Biol Chem 281: 20–26.

  • Ongusaha PP, Ouchi T, Kim KT, Nytko E, Kwak JC, Duda RB et al. (2003). Oncogene 22: 3749–3758.

  • Ouchi T, Lee SW, Ouchi M, Aaronson SA, Horvath CM . (2000). Proc Natl Acad Sci USA 97: 5208–5213.

  • Pao GM, Janknecht R, Ruffner H, Hunter T, Verma IM . (2000). Proc Natl Acad Sci USA 97: 1020–1025.

  • Quinn JE, Kennedy RD, Mullan PB, Gilmore PM, Carty M, Johnston PG et al. (2003). Cancer Res 63: 6221–6228.

  • Razandi M, Pedram A, Rosen EM, Levin ER . (2004). Mol Cell Biol 24: 5900–5913.

  • Ree AH, Bratland A, Nome RV, Stokke T, Fodstad O . (2003). Oncogene 22: 8952–8955.

  • Schaeper U, Subramanian T, Lim L, Boyd JM, Chinnadurai G . (1998). J Biol Chem 273: 8549–8552.

  • Scully R, Anderson SF, Chao DM, Wei W, Ye L, Young RA et al. (1997). Proc Natl Acad Sci USA 94: 5605–5610.

  • Somasundaram K, MacLachlan TK, Burns TF, Sgagias M, Cowan KH, Weber BL et al. (1999). Oncogene 18: 6605–6614.

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

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

  • Tan W, Kim S, Boyer TG . (2004a). J Biol Chem 279: 55153–55160.

  • Tan W, Zheng L, Lee WH, Boyer TG . (2004b). J Biol Chem 279: 6576–6587.

  • Wada O, Oishi H, Takada I, Yanagisawa J, Yano T, Kato S . (2004). Oncogene 23: 6000–6005.

  • Wang C, Fan S, Li Z, Fu M, Rao M, Ma Y et al. (2005). Cancer Res 65: 6557–6567.

  • Wang Q, Zhang H, Kajino K, Greene MI . (1998). Oncogene 17: 1939–1948.

  • Wang RH, Yu H, Deng CX . (2004). Proc Natl Acad Sci USA 101: 17108–17113.

  • Wang XW, Zhan Q, Coursen JD, Khan MA, Kontny HU, Yu L et al. (1999). Proc Natl Acad Sci USA 96: 3706–3711.

  • Welcsh PL, Lee MK, Gonzalez-Hernandez RM, Black DJ, Mahadevappa M, Swisher EM et al. (2002). Proc Natl Acad Sci USA 99: 7560–7565.

  • Williams RS, Glover JN . (2003). J Biol Chem 278: 2630–2635.

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

  • Wong AK, Ormonde PA, Pero R, Chen Y, Lian L, Salada G et al. (1998). Oncogene 17: 2279–2285.

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

  • Wu-Baer F, Baer R . (2001). Nature 414: 36.

  • Xiong J, Fan S, Meng Q, Schramm L, Wang C, Bouzahza B et al. (2003). Mol Cell Biol 23: 8668–8690.

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

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

  • Xu J, Fan S, Rosen EM . (2005). Endocrinology 146: 2031–2047.

  • Yarden RI, Brody LC . (1999). Proc Natl Acad Sci USA 96: 4983–4988.

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

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

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

  • Yu X, Wu LC, Bowcock AM, Aronheim A, Baer R . (1998). J Biol Chem 273: 25388–25392.

  • Yun J, Lee WH . (2003). Mol Cell Biol 23: 7305–7314.

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

  • Zhang X, Krutchinsky A, Fukuda A, Chen W, Yamamura S, Chait BT et al. (2005). Mol Cell 19: 89–100.

  • Zheng L, Annab LA, Afshari CA, Lee WH, Boyer TG . (2001). Proc Natl Acad Sci USA 98: 9587–9592.

  • Zheng L, Pan H, Li S, Flesken-Nikitin A, Chen PL, Boyer TG et al. (2000). Mol Cell 6: 757–768.

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

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Acknowledgements

We would like to apologise to any colleagues in the BRCA1 field whose work has not been included in this review due to space restrictions.

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Correspondence to D P Harkin.

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Mullan, P., Quinn, J. & Harkin, D. The role of BRCA1 in transcriptional regulation and cell cycle control. Oncogene 25, 5854–5863 (2006). https://doi.org/10.1038/sj.onc.1209872

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Keywords

  • BRCA1
  • transcription
  • cell cycle

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