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Conserved BRCT regions of TopBP1 and of the tumor suppressor BRCA1 bind strand breaks and termini of DNA

Oncogene volume 18, pages 5194–5203 (1999)Cite this article

Abstract

The BRCT region, the carboxyl-terminus of BRCA1 (the breast cancer susceptibility gene 1 product), is a ubiquitous region homologous to regions in DNA repair enzymes and cell cycle regulators. We showed that the BRCT regions bound DNA fragments, using the TopBP1 protein (topoisomerase II binding protein 1), with eight BRCTs as a model protein. The bindings were independent of DNA sequences, forms of DNA termini and energy. The BRCT-DNA complex showed resistance to an exonuclease, indicating that BRCT bound DNA breaks. The BRCTs also bound DNA nicks, suggesting that BRCTs play an important role in detection of both single- and double-strand DNA breaks or ends. On the other hand, BRCTs did not bind circular intact DNA. BRCTs of BRCA1 also bound DNA termini. Since some BRCTs are unique general elements in some tumor suppressions, these findings will reveal novel aspects of the tumor suppression mechanism.

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References

  • Birnboim HC and Doly J. . 1979 Nucl. Acids Res. 7: 1513–1523.

  • Blier PR, Griffith AJ, Craft J and Hardin JA. . 1993 J. Biol. Chem. 268: 7594–7601.

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

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

  • Cranston A, Bocker T, Reitmair A, Palazzo J, Wilson T, Mak T and Fishel R. . 1997 Nat. Genet. 17: 114–118.

  • Furnari B, Rhind N and Russell P. . 1997 Science 277: 1495–1497.

  • Gyuris J, Golemis E, Chertkov H and Brent R. . 1993 Cell 75: 791–803.

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

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

  • Kubota Y, Nash RA, Klungland A, Schar P, Barnes DE and Lindahl T. . 1996 EMBO J. 15: 6662–6670.

  • Laemmli UK. . 1970 Nature 227: 680–685.

  • Miki T, Smith CL, Long JE, Eva A and Fleming TP. . 1993 Nature 362: 462–465.

  • Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, Liu Q, Cochran C, Bennett LM, Ding W, Bell R, Rosenthal J, Hyssey 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, Dayanath P, Ward J, Tonin P, Narod S, Bristow P, Norris F, 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 M. . 1994 Science 266: 66–71.

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

  • Saka Y, Esashi F, Matsusaka T, Mochida S and Yanagida M. . 1997 Genes Dev. 11: 3387–3400.

  • Saka Y, Fantes P, Sutani T, McInerny C, Creanor J and Yanagida M. . 1994 EMBO J. 13: 5319–5329.

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

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

  • Shen MR, Zdzienicka MZ, Mohrenweiser H, Thompson LH and Thelen MP. . 1998 Nucl. Acids Res. 26: 1032–1037.

  • Sherr CJ. . 1996 Science 274: 1672–1677.

  • Thukral SK, Blain GC, Chang KK and Fields S. . 1994 Mol. Cell Biol. 14: 8315–8321.

  • Varon R, Vissinga C, Platzer M, Cerosaletti KM, Chrzanowska KH, Saar K, Beckmann G, Seemanova E, Cooper PR, Nowak NJ, Stumm M, Weemaes CMR, Gatti RA, Wilson RK, Digweed M, Rosenthal A, Sperling K, Concannon P and Reis A. . 1998 Cell 93: 467–476.

  • Vieira J and Messing J. . 1982 Gene 19: 259–268.

  • Wu X and Lieber MR. . 1996 Mol. Cell Biol. 16: 5186–5193.

  • Yamane K, Kawabata M and Tsuruo T. . 1997 Eur. J. Biochem. 250: 794–799.

  • Yamane K and Mizushima S. . 1988 J. Biol. Chem. 263: 19690–19696.

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Acknowledgements

This study was supported by the Program for Promotion of Fundamental Studies in Health Sciences of the Organization for Pharmaceutical Safety and Research of Japan, and by Grant 09760301 (to K Yamane) from the Ministry of Education, Science and Culture, Japan.

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Authors and Affiliations

  1. Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo, 113-0032, Japan

    Kazuhiko Yamane & Takashi Tsuruo

  2. Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 1-37-1, Kami-Ikebukuro, Toshima-ku, Tokyo, 170-8455, Japan

    Kazuhiko Yamane & Takashi Tsuruo

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  1. Kazuhiko Yamane
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Yamane, K., Tsuruo, T. Conserved BRCT regions of TopBP1 and of the tumor suppressor BRCA1 bind strand breaks and termini of DNA. Oncogene 18, 5194–5203 (1999). https://doi.org/10.1038/sj.onc.1202922

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