53BP1, a mediator of the DNA damage checkpoint.
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.
D019313:BRCA1 Protein / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism; D064447:Checkpoint Kinase 2; D004247:DNA / Q000096:biosynthesis; D004249:DNA Damage; D016195:G2 Phase; D006657:Histones / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008938:Mitosis; D009687:Nuclear Proteins / Q000378:metabolism; D010750:Phosphoproteins; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D034741:RNA, Small Interfering; D011839:Radiation, Ionizing; D016196:S Phase; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D000071857:Tumor Suppressor p53-Binding Protein 1
D019313:BRCA1 Protein; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins; D010750:Phosphoproteins; D034741:RNA, Small Interfering; C498301:TP53BP1 protein, human; D016159:Tumor Suppressor Protein p53; D000071857:Tumor Suppressor p53-Binding Protein 1; D004247:DNA; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases