An investigation into 53BP1 complex formation.
Loss of the control over cellular proliferation can lead to cell death or result in the abnormal proliferation characteristic of the cancerous state. Among the controls used to achieve normal cellular proliferation is the DNA damage checkpoint pathway that monitors genome integrity (Hartwell and Kastan 1994). 53BP1 was identified as a protein that interacts with the DNA-binding core domain of the tumor suppressor p53. The p53-binding region of 53BP1 maps to the C-terminal BRCT domains which are homologous to those found in the breast cancer protein BRCA1 and in other proteins involved in the DNA damage response, notably budding yeast Rad9. In addition to its recently reported role in sensing double strand breaks, 53BP1 is believed to have roles, currently ill understood, in many aspects of DNA metabolism ranging from transcription and class switch recombination to 'mediating' the DNA damage checkpoint response (Chai et al. 1999; Huyen et al. 2004; Sengupta et al. 2004; Ward et al. 2004). Here, we investigate 53BP1 complex formation. We investigate 53BP1 oligomerization and show that this is not dependent on the presence of disulfide bridges.
Roche
Kevin C
KC
National University of Ireland Galway, Department of Biochemistry. kevin.roche@nuigalway.ie
Lowndes
Noel F
NF
D048868:Adaptor Proteins, Signal Transducing; D064007:Ataxia Telangiectasia Mutated Proteins; D019313:BRCA1 Protein / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000378:metabolism; D004220:Disulfides / Q000737:chemistry; D016158:Genes, p53; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D011485:Protein Binding; D011489:Protein Denaturation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011995:Recombination, Genetic; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D000071857:Tumor Suppressor p53-Binding Protein 1
D048868:Adaptor Proteins, Signal Transducing; D019313:BRCA1 Protein; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D004220:Disulfides; D047908:Intracellular Signaling Peptides and Proteins; C413163:MDC1 protein, human; D009687:Nuclear Proteins; C498301:TP53BP1 protein, human; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins; D000071857:Tumor Suppressor p53-Binding Protein 1; C069930:rad9 protein; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases