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Originally published in Science Express on 3 October 2002
Science 15 November 2002:
Vol. 298. no. 5597, pp. 1435 - 1438
DOI: 10.1126/science.1076182
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Reports

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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