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Science 298 (5597): 1435-1438

Copyright © 2002 by the American Association for the Advancement of Science

53BP1, a Mediator of the DNA Damage Checkpoint

Bin Wang,1 Shuhei Matsuoka,1 Phillip B. Carpenter,4 Stephen J. Elledge123*

53BP1 binds to the tumor suppressor protein p53 and has a potential role in DNA damage responses. We used small interfering RNA (siRNA) directed against 53BP1 in mammalian cells to demonstrate that 53BP1 is a key transducer of the DNA damage checkpoint signal. 53BP1 was required for p53 accumulation, G2-M checkpoint arrest, and the intra-S-phase checkpoint in response to ionizing radiation. 53BP1 played a partially redundant role in phosphorylation of the downstream checkpoint effector proteins Brca1 and Chk2 but was required for the formation of Brca1 foci in a hierarchical branched pathway for the recruitment of repair and signaling proteins to sites of DNA damage.

1 Verna and Mars McLean Department of Biochemistry and Molecular Biology,
2 Department of Molecular and Human Genetics,
3 Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA.
4 Department of Biochemistry and Molecular Biology, University of Texas Health Sciences Center, Houston, TX 77030, USA.
*   To whom correspondence should be addressed. E-mail: selledge{at}bcm.tmc.edu



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X. Zhang, J. Succi, Z. Feng, S. Prithivirajsingh, M. D. Story, and R. J. Legerski (2004)
Mol. Cell. Biol. 24, 9207-9220
   Abstract »    Full Text »    PDF »
Functional interaction between BLM helicase and 53BP1 in a Chk1-mediated pathway during S-phase arrest.
S. Sengupta, A. I. Robles, S. P. Linke, N. I. Sinogeeva, R. Zhang, R. Pedeux, I. M. Ward, A. Celeste, A. Nussenzweig, J. Chen, et al. (2004)
J. Cell Biol. 166, 801-813
   Abstract »    Full Text »    PDF »
Homo-oligomerization Is the Essential Function of the Tandem BRCT Domains in the Checkpoint Protein Crb2.
L.-L. Du, B. A. Moser, and P. Russell (2004)
J. Biol. Chem. 279, 38409-38414
   Abstract »    Full Text »    PDF »
Human Rif1, ortholog of a yeast telomeric protein, is regulated by ATM and 53BP1 and functions in the S-phase checkpoint.
J. Silverman, H. Takai, S. B.C. Buonomo, F. Eisenhaber, and T. de Lange (2004)
Genes & Dev. 18, 2108-2119
   Abstract »    Full Text »    PDF »
Dynamic targeting of the replication machinery to sites of DNA damage.
D. A. Solomon, M. C. Cardoso, and E. S. Knudsen (2004)
J. Cell Biol. 166, 455-463
   Abstract »    Full Text »    PDF »

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