Role for the BRCA1 C-terminal Repeats (BRCT) Protein 53BP1 in Maintaining Genomic Stability
| Autor: | Zhenfang Xia, Rodney E. Kellems, Stephen J. Elledge, Bin Wang, Phillip B. Carpenter, Julio C. Morales, Tao Lu, Walter N. Hittelman, Corina Rosales, Melissa B. Aldrich |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Small interfering RNA
DNA Repair Chromosomal Proteins Non-Histone DNA damage DNA repair T cell Active Transport Cell Nucleus Growth Biology Biochemistry Autoimmune Diseases law.invention Mice Immune system law In vivo medicine Animals Molecular Biology Chromosome Aberrations Mice Knockout Genome BRCA1 Protein Intracellular Signaling Peptides and Proteins Terminal Repeat Sequences Cell Biology Phosphoproteins Molecular biology DNA-Binding Proteins Disease Models Animal medicine.anatomical_structure Phosphorylation Suppressor Carrier Proteins Tumor Suppressor p53-Binding Protein 1 DNA Damage |
| Zdroj: | Journal of Biological Chemistry. 278:14971-14977 |
| ISSN: | 0021-9258 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|