53BP1, a mediator of the DNA damage checkpoint.
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Wang B, Matsuoka S, Carpenter PB, Elledge SJ
53BP1, a mediator of the DNA damage checkpoint.
Science. 2002 Nov 15;298(5597):1435-8. Epub 2002 Oct 3.
- PubMed ID
- 12364621 [ View in PubMed]
- Abstract
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.