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Bin Wang,1Shuhei Matsuoka,1Phillip B. Carpenter,4Stephen J. Elledge123*
53BP1 binds to the tumor suppressor protein p53 and has
a potential role in DNA damage responses. We used small interferingRNA
(siRNA) directed against 53BP1 in mammalian cells to demonstratethat
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
ofthe downstream checkpoint effector proteins Brca1 and Chk2 butwas
required for the formation of Brca1 foci in a hierarchicalbranched
pathway for the recruitment of repair and signaling proteinsto 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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