Abstract
The BRCT region, the carboxyl-terminus of BRCA1 (the breast cancer susceptibility gene 1 product), is ubiquitous in several proteins that participate in cell cycle checkpoints and DNA repair. We have previously shown that the BRCT regions of TopBP1 (DNA topoisomerase II binding protein 1) and BRCA1 bound DNA breaks. A BRCT-related region, BRCT-W1, in the retinoblastoma susceptibility gene product (Rb) also could bind DNA fragments, independently of DNA sequences. Five BRCT-W regions were found in the Rb family. All BRCT-Ws of Rb bound DNA fragments. Electron microscopy and treatment with an exonuclease showed that BRCT-Ws bound double-strand DNA breaks. Since some BRCTs are exceptional common relating elements in tumor suppression, our findings reveal novel aspects of the tumor suppression mechanism.
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References
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: 25–23
Chai YL, Cui J, Shao N, Shyam E, Reddy P and Rao VN . 1999 Oncogene 18: 263–268
Cranston A, Bocker T, Reitmair A, Palazzo J, Wilson T, Mak T and Fishel R . 1997 Nat Genet 17: 114–118
de Vries E, van Driel W, Bergsma WG, Arnberg AC and van der Vliet PC . 1989 J Mol Biol 208: 65–78
Ewen ME, Xing YG, Lawrence JB and Livingston DM . 1991 Cell 66: 1155–1164
Field SJ, Tsai FY, Kuo F, Zubiaga AM, Kaelin Jr WG, Livingston DM, Orkin SH and Greenberg ME . 1996 Cell 85: 549–561
Gowen LC, Avrutskaya AV, Latour AM, Koller BH and Leadon SA . 1998 Science 281: 1009–1012
Harrington EA, Bruce JL, Harlow E and Dyson N . 1998 Proc Natl Acad Sci USA 95: 11945–11950
Hensey CE, Hong F, Durfee T, Qian YW, Lee EY and Lee WH . 1994 J Biol Chem 269: 1380–1387
Hu QJ, Dyson N and Harlow E . 1990 EMBO J 9: 1147–1155
Huang S, Wang NP, Tseng BY, Lee WH and Lee EH . 1990 EMBO J 9: 1815–1822
Ito K, Liu X, Katayama E and Uyeda TQ . 1999 Biophys J 76: 985–992
Kaelin Jr, WG, Ewen ME and Livingston DM . 1990 Mol Cell Biol 10: 3761–3769
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
Kurosaki T, Ushiro H, Mitsuuchi Y, Suzuki S, Matsuda M, Matsuda Y, Katunuma N, Kangawa K, Matsuo H, Hirose T, Inayama S and Shizuta Y . 1987 J Biol Chem 262: 15990–15997
Laemmli UK . 1970 Nature 227: 680–685
Lee JO, Russo AA and Pavletich NP . 1998 Nature 391: 859–865
Lee S, Elenbaas B, Levine A and Griffith J . 1995 Cell 81: 1013–1020
Lee WH, Shew JY, Hong FD, Sery TW, Donoso LA, Young LJ, Bookstein R and Lee EY . 1987 Nature 329: 642–645
Li Y, Graham C, Lacy S, Duncan AM and Whyte P . 1993 Genes Dev 7: 2366–2377
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
Mimori T and Hardin JA . 1986 J Biol Chem 261: 10375–10379
Molinete M, Vermeulen W, Burkle A, Menissier-de Murcia J, Kupper JH, Hoeijmakers JH and de Murcia G . 1993 EMBO J 12: 2109–2117
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
Sterner JM, Dew-Knight S, Musahl C, Kornbluth S and Horowitz JM . 1998 Mol Cell Biol 18: 2748–2757
Tan X and Wang JY . 1998 Trends Cell Biol 8: 116–120
Thukral SK, Blain GC, Chang KK and Fields S . 1994 Mol Cell Biol 14: 8315–8321
Van Dyck E, Stasiak AZ, Stasiak A and West SC . 1999 Nature 398: 728–731
Vieira J and Messing J . 1982 Gene 19: 259–268
Wang J, Guo K, Wills KN and Walsh K . 1997 Cancer Res 57: 351–354
Wang NP, Chen PL, Huang S, Donoso LA, Lee WH and Lee EY . 1990 Cell Growth Differ 1: 233–239
Weinberg RA . 1995 Cell 81: 323–330
Yamane K, Kawabata M and Tsuruo T . 1997 Eur J Biochem 250: 794–799
Yamane K and Tsuruo T . 1999 Oncogene 18: 5194–5203
Yamasaki L, Jacks T, Bronson R, Goillot E, Harlow E and Dyson NJ . 1996 Cell 85: 537–548
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. K Yamane was a postdoctoral fellow supported by the program. This work is also supported by a special grant for Advanced Research on Cancer from Ministry of Education Science, Sports and Culture, Japan.
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Yamane, K., Katayama, E., Sugasawa, K. et al. Retinoblastoma susceptibility protein, Rb, possesses multiple BRCT-Ws, BRCA1 carboxyl-terminus-related W regions with DNA break-binding activity. Oncogene 19, 1982–1991 (2000). https://doi.org/10.1038/sj.onc.1203528
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DOI: https://doi.org/10.1038/sj.onc.1203528