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DSS1 is required for the stability of BRCA2

Oncogene volume 25, pages 1186–1194 (2006)Cite this article

Abstract

DSS1 is an evolutionarily conserved acidic protein that binds to BRCA2. However, study of the function of DSS1 in mammalian cells has been hampered because endogenous DSS1 has not been detectable by Western blotting. Here, we developed a modified Western blotting protocol that detects endogenous DSS1 protein, and used it to study the function of DSS1 and its interaction with BRCA2 in mammalian cells. We found that essentially all BRCA2 in human cell lines is associated with DSS1. Importantly, we found that RNAi knockdown of DSS1 in human cell lines led to dramatic loss of BRCA2 protein, mainly due to its increased degradation. Furthermore, the stability of BRCA2 mutant devoid of the DSS1-binding domain is unaffected by the depletion of DSS1. Most notably, like BRCA2 depletion, DSS1 depletion also led to hypersensitivity to DNA damage. These results demonstrated that the stability of BRCA2 protein in mammalian cells depends on the presence of DSS1. Deletion or mutation of DSS1 or suppression of its expression by other mechanisms are therefore potential causative mechanisms for human breast and ovarian cancer. Such mechanisms may be relevant to sporadic as well as familiar breast cancer where BRCA1 and BRCA2 mutations are not present.

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References

  • Band V, Sager R . (1989). Proc Natl Acad Sci USA 86: 1249–1253.

  • Boring CC, Squires TS, Tong T . (1991). CA Cancer J Clin 41: 19–36.

  • Brody LC, Biesecker BB . (1998). Medicine (Baltimore) 77: 208–226.

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

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

  • Connor F, Bertwistle D, Mee PJ, Ross GM, Swift S, Grigorieva E et al. (1997). Nat Genet 17: 423–430.

  • 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.

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

  • Dimri GP, Itahana K, Acosta M, Campisi J . (2000). Mol Cell Biol 20: 273–285.

  • Goldman LA, Cutrone EC, Kotenko SV, Krause CD, Langer JA . (1996). Biotechniques 21: 1013–1015.

  • Gudmundsdottir K, Lord CJ, Witt E, Tutt AN, Ashworth A . (2004). EMBO Rep 5: 989–993 [E-pub 2004 September 10].

  • Howlett NG, Taniguchi T, Olson S, Cox B, Waisfisz Q, De Die-Smulders C et al. (2002). Science 297: 606–609 [E-pub 2002 June 13].

  • Hughes-Davies L, Huntsman D, Ruas M, Fuks F, Bye J, Chin SF et al. (2003). Cell 115: 523–535.

  • Isono E, Saeki Y, Yokosawa H, Toh-e A . (2004). J Biol Chem 279: 27168–27176 [E-pub 2004 April 21].

  • Jantti J, Lahdenranta J, Olkkonen VM, Soderlund H, Keranen S . (1999). Proc Natl Acad Sci USA 96: 909–914.

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

  • 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.

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

  • Milner J, Ponder B, Hughes-Davies L, Seltmann M, Kouzarides T . (1997). Nature 386: 772–773.

  • Mizuta R, LaSalle JM, Cheng HL, Shinohara A, Ogawa H, Copeland N et al. (1997). Proc Natl Acad Sci USA 94: 6927–6932.

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

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

  • Rahman N, Stratton MR . (1998). Annu Rev Genet 32: 95–121.

  • Ratsch SB, Gao Q, Srinivasan S, Wazer DE, Band V . (2001). Radiat Res 155: 143–150.

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

  • Sharan SK, Pyle A, Coppola V, Babus J, Swaminathan S, Benedict J et al. (2004). Development 131: 131–142.

  • Shin S, Verma IM . (2003). Proc Natl Acad Sci USA 100: 7201–7206 [E-pub 2003 May 19].

  • Sone T, Saeki Y, Toh-e A, Yokosawa H . (2004). J Biol Chem 279: 28807–28816 [E-pub 2004 April 26].

  • Tavtigian SV, Simard J, Rommens J, Couch F, Shattuck-Eidens D, Neuhausen S et al. (1996). Nat Genet 12: 333–337.

  • Tian XX, Rai D, Li J, Zou C, Bai Y, Wazer D et al. (2005). Cancer Res 65: 4747–4753.

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

  • Wang SC, Makino K, Su LK, Pao AY, Kim JS, Hung MC . (2001). Cancer Res 61: 2838–2842.

  • Wang SC, Shao R, Pao AY, Zhang S, Hung MC, Su LK . (2002). Cancer Res 62: 1311–1314.

  • Wei SJ, Trempus CS, Cannon RE, Bortner CD, Tennant RW . (2003). J Biol Chem 278: 1758–1768 [E-pub 2002 November 4].

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

  • Wooster R, Bignell G, Lancaster J, Swift S, Seal S, Mangion J et al. (1995). Nature 378: 789–792.

  • Wooster R, Neuhausen SL, Mangion J, Quirk Y, Ford D, Collins N et al. (1994). Science 265: 2088–2090.

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

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

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Acknowledgements

We thank Dr Wen-Hwa Lee, Dr Phang-Lang Chen, and Dr Inder M Verma for providing us with the full-length BRCA2 construct. We thank Dr Hamid Band, Goberdhan Dimri, and members of Gao's laboratory for their critical reading of this manuscript. This work was supported by grants from the National Institutes of Health (1 R01 CA095221-01A1 and 1 R01 CA96986-01A1) and the American Cancer Society (RSG-03-048-01) to Qingshen Gao.

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Authors and Affiliations

  1. Division of Cancer Biology, Department of Medicine, Evanston Northwestern Healthcare Research Institute, Northwestern University Feinberg School of Medicine, Evanston, IL, USA

    J Li, C Zou, V Band & Q Gao

  2. Department of Radiation Oncology, New England Medical Center, Tufts University School of Medicine, Boston, MA, USA

    Y Bai & D E Wazer

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  1. J Li
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  2. C Zou
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  6. Q Gao
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Correspondence to Q Gao.

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Li, J., Zou, C., Bai, Y. et al. DSS1 is required for the stability of BRCA2. Oncogene 25, 1186–1194 (2006). https://doi.org/10.1038/sj.onc.1209153

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