| First Author | Morales JC | Year | 2003 |
| Journal | J Biol Chem | Volume | 278 |
| Issue | 17 | Pages | 14971-7 |
| PubMed ID | 12578828 | Mgi Jnum | J:83164 |
| Mgi Id | MGI:2657092 | Doi | 10.1074/jbc.M212484200 |
| Citation | Morales JC, et al. (2003) Role for the BRCA1 C-terminal repeats (BRCT) protein 53BP1 in maintaining genomic stability. J Biol Chem 278(17):14971-7 |
| abstractText | p53-binding protein-1 (53BP1) is phosphorylated in response to DNA damage and rapidly relocalizes to presumptive sites of DNA damage along with Mre11 and the phosphorylated histone 2A variant, gamma-H2AX. 53BP1 associates with the BRCA1 tumor suppressor, and knock-down experiments with small interfering RNA have revealed a role for the protein in the checkpoint response to DNA damage. By generating mice defective in m53BP1 (m53BP1(tr/tr)), we have created an animal model to further explore its biochemical and genetic roles in vivo. We find that m53BP1(tr/tr) animals are growth-retarded and show various immune deficiencies including a specific reduction in thymus size and T cell count. Consistent with a role in responding to DNA damage, we find that m53BP1(tr/tr) mice are sensitive to ionizing radiation (gamma-IR), and cells from these animals exhibit chromosomal abnormalities consistent with defects in DNA repair. Thus, 53BP1 is a critical element in the DNA damage response and plays an integral role in maintaining genomic stability. |
