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.

  • Original Paper
  • Published:

Adenosine nucleotide modulates the physical interaction between hMSH2 and BRCA1

Oncogene volume 20, pages 4640–4649 (2001) Cite this article

View saved research

Abstract

We have identified the physical interaction between the Breast Cancer susceptibility gene product BRCA1 and the Hereditary Non-Polyposis Colorectal Cancer (HNPCC) and DNA mismatch repair (MMR) gene product hMSH2, both in vitro and in vivo. The BRCA1-hMSH2 association involved several well-defined regions of both proteins which include the adenosine nucleotide binding domain of hMSH2. Moreover, the interaction of BRCA1 with purified hMSH2-hMSH6 appears to be modulated by adenosine nucleotide much like G protein downstream interaction/signaling is modulated by guanosine nucleotide. BARD1, another BRCA1-interacting protein, was also found to interact with hMSH2. In addition, BRCA1 was found to associate with both hMSH3 and hMSH6, the heterodimeric partners of hMSH2. These observations implicate BRCA1/BARD1 as downstream effectors of the adenosine nucleotide-activated hMSH2-hMSH6 signaling complex, and suggest a global role for BRCA1 in DNA damage processing. The functional interaction between BRCA1 and hMSH2 may provide a partial explanation for the background of gynecological and colorectal cancer in both HNPCC and BRCA1 kindreds, respectively.

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

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

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

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

Explore related subjects

Discover the latest articles and news in related subjects.

Abbreviations

MMR:

mismatch repair

TCR:

transcription-coupled DNA damage repair

References

  • Acharya S, Wilson T, Gradia S, Kane MF, Guerrette S, Marsischky GT, Kolodner R, Fishel R . 1996 Proc. Natl. Acad. Sci. USA 93: 13629–13634

  • Amundson SA, Zhan Q, Penn LZ, Fornace Jr AJ . 1998 Oncogene 17: 2149–2154

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

  • Bush A, Mateyak M, Dugan K, Obaya A, Adachi S, Sedivy J, Cole M . 1998 Genes. Dev. 12: 3797–3802

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

  • Chapman MS, Verma IM . 1996 Nature 382: 678–679

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

  • Couch FJ, DeShano ML, Blackwood MA, Calzone K, Stopfer J, Campeau L, Ganguly A, Rebbeck T, Weber BL . 1997 N. Engl. J. Med. 336: 1409–1415

  • de Boer J, Donker I, de Wit J, Hoeijmakers JH, Weeda G . 1998 Cancer Res. 58: 89–94

  • Dietmaier W, Wallinger S, Bocker T, Kullmann F, Fishel R, Ruschoff J . 1997 Cancer Res. 57: 4749–4756

  • Drummond JT, Anthoney A, Brown R, Modrich P . 1996 J. Biol. Chem. 271: 19645–19648

  • Drummond JT, Li GM, Longley MJ, Modrich P . 1995 Science 268: 1909–1912

  • Easton DF, Ford D, Bishop DT . 1995 Am. J. Hum. Genet. 56: 265–271

  • Fishel R . 1998 Genes. Dev. 12: 2096–2101

  • Fishel R . 1999 Nat. Med. 5: 1239–1241

  • Fishel R, Ewel A, Lescoe MK . 1994 Cancer Res. 54: 5539–5542

  • Fishel R, Lescoe MK, Rao MR, Copeland NG, Jenkins NA, Garber J, Kane M, Kolodner R . 1993 Cell 75: 1027–1038

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

  • Gradia S, Acharya S, Fishel R . 1997 Cell 91: 995–1005

  • Gradia S, Acharya S, Fishel R . 2000 J. Biol. Chem. 275: 3922–3930

  • Gradia S, Subramanian D, Wilson T, Acharya S, Makhov A, Griffith J, Fishel R . 1999 Mol. Cell 3: 255–261

  • Guerrette S, Acharya S, Fishel R . 1999 J. Biol. Chem. 274: 6336–6341

  • Guerrette S, Wilson T, Gradia S, Fishel R . 1998 Mol. Cell. Biol. 18: 6616–6623

  • Hanawalt PC . 1994 Science 266: 1957–1958

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

  • Jensen RA, Thompson ME, Jetton TL, Szabo CI, van der Meer R, Helou B, Tronick SR, Page DL, King MC, Holt JT . 1996 Nat. Genet. 12: 303–308

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

  • Lynch HT, Smyrk T, Lynch J . 1997 Cancer Genet. Cytogenet. 93: 84–99

  • Maldonado E, Shiekhattar R, Sheldon M, Cho H, Drapkin R, Rickert P, Lees E, Anderson CW, Linn S, Reinberg D . 1996 Nature 381: 86–89

  • Marhin WW, Chen S, Facchini LM, Fornace Jr. AJ, Penn LZ . 1997 Oncogene 14: 2825–2834

  • Mello JA, Acharya S, Fishel R, Essigmann JM . 1996 Chem. Biol. 3: 579–589

  • Mellon I, Rajpal DK, Koi M, Boland CR, Champe GN . 1996 Science 272: 557–560

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

  • Neuhausen SL, Marshall CJ . 1994 Cancer Res. 54: 6069–6072

  • Peltomaki P, Vasen HF . 1997 Gastroenterology 113: 1146–1158

  • Ruffner H, Jiang W, Craig AG, Hunter T, Verma IM . 1999 Mol. Cell. Biol. 19: 4843–4854

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

  • Sancar A . 1994 Science 266: 1954–1956

  • Schmutte C, Marinescu RC, Sadoff MM, Guerrette S, Overhauser J, Fishel R . 1998 Cancer Res. 58: 4537–4542

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

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

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

  • Somasundaram K, Zhang H, Zeng YX, Houvras Y, Peng Y, Wu GS, Licht JD, Weber BL, El-Deiry WS . 1997 Nature 389: 187–190

  • Struewing JP, Hartge P, Wacholder S, Baker SM, Berlin M, McAdams M, Timmerman MM, Brody LC, Tucker MA . 1997 N. Engl. J. Med. 336: 1401–1408

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

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

  • Wilson CA, Payton MN, Pekar SK, Zhang K, Pacifici RE, Gudas JL, Thukral S, Calzone FJ, Reese DM, Slamon DI . 1996 Nat. Genet. 13: 264–265

  • Wilson T, Guerrette S, Fishel R . 1999 J. Biol. Chem. 274: 21659–21664

  • Wilson TM, Ewel A, Duguid JR, Eble JN, Lescoe MK, Fishel R, Kelley MR . 1995 Cancer Res. 55: 5146–5150

  • Wong AK, Ormonde PA, Pero R, Chen Y, Lian L, Salada G, Berry S, Lawrence Q, Dayananth P, Ha P, Tavtigian SV, Teng DH, Bartel PL . 1998 Oncogene 17: 2279–2285

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

  • Zhang H, Richards B, Wilson T, Lloyd M, Cranston A, Thorburn A, Fishel R, Meuth M . 1999 Cancer Res. 59: 3021–3027

  • Zhang H, Somasundaram K, Peng Y, Tian H, Bi D, Weber BL, El-Deiry WS . 1998 Oncogene 16: 1713–1721

  • Zhang HT, Zhang X, Zhao HZ, Kajino Y, Weber BL, Davis JG, Wang Q, O'Rourke DM, Zhang HB, Kajino K, Greene MI . 1997 Oncogene 14: 2863–2869

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

Download references

Acknowledgements

We thank Dr Barbara Weber for pCR3-BRCA1, Drs Gideon Dreyfuss, Qing Liu and Lili Wan for the support on the yeast two-hybrid system, Hansjuerg Alder and the members of the Sidney Kimmel Nucleic Acid Facility for nucleotide synthesis and sequencing, Christoph Schmutte for help in preparing the Figures for this manuscript, Samir Acharya, Scott Gradia, and Greg Tombline for helpful discussions. This work was supported by grants from the Abramson Family Cancer Research Institute, CaPCURE, NIH, and the U.S. Army (MI Greene) and NIH/NCI (R Fishel).

Author information

Author notes

  1. Qiang Wang, Hongtao Zhang and Shawn Guerrette: Q Wang, H Zhang and S Guerrette contributed equally to this work

Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, The Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, 19104, Pennsylvania, PA, USA

    Qiang Wang, Hongtao Zhang, Jinqiu Chen & Mark I Greene

  2. Department of Microbiology and Immunology, Genetics and Molecular Biology Program, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, 19107, Pennsylvania, PA, USA

    Shawn Guerrette, Anthony Mazurek, Teresa Wilson & Richard Fishel

  3. Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, 19122, Pennsylvania, PA, USA

    Artur Slupianek & Tomasz Skorski

Authors
  1. Qiang Wang
    View author publications

    Search author on:PubMed Google Scholar

  2. Hongtao Zhang
    View author publications

    Search author on:PubMed Google Scholar

  3. Shawn Guerrette
    View author publications

    Search author on:PubMed Google Scholar

  4. Jinqiu Chen
    View author publications

    Search author on:PubMed Google Scholar

  5. Anthony Mazurek
    View author publications

    Search author on:PubMed Google Scholar

  6. Teresa Wilson
    View author publications

    Search author on:PubMed Google Scholar

  7. Artur Slupianek
    View author publications

    Search author on:PubMed Google Scholar

  8. Tomasz Skorski
    View author publications

    Search author on:PubMed Google Scholar

  9. Richard Fishel
    View author publications

    Search author on:PubMed Google Scholar

  10. Mark I Greene
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to Richard Fishel.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, Q., Zhang, H., Guerrette, S. et al. Adenosine nucleotide modulates the physical interaction between hMSH2 and BRCA1. Oncogene 20, 4640–4649 (2001). https://doi.org/10.1038/sj.onc.1204625

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/sj.onc.1204625

Keywords

Search

Advanced search

Quick links