PT - JOURNAL ARTICLE AU - Wang, Bin AU - Matsuoka, Shuhei AU - Carpenter, Phillip B. AU - Elledge, Stephen J. TI - 53BP1, a Mediator of the DNA Damage Checkpoint AID - 10.1126/science.1076182 DP - 2002 Nov 15 TA - Science PG - 1435--1438 VI - 298 IP - 5597 4099 - http://science.sciencemag.org/content/298/5597/1435.short 4100 - http://science.sciencemag.org/content/298/5597/1435.full SO - Science2002 Nov 15; 298 AB - 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.