Role for the BRCA1 C-terminal Repeats (BRCT) Protein 53BP1 in Maintaining Genomic Stability
Copyright policy )Role for the BRCA1 C-terminal Repeats (BRCT) Protein 53BP1 in Maintaining Genomic Stability
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.
- Baylor College of Medicine United States
- Howard Hughes Medical Institute United States
- The University of Texas MD Anderson Cancer Center United States
- The University of Texas System United States
- The University of Texas Health Science Center at Houston United States
Chromosome Aberrations, Mice, Knockout, Genome, DNA Repair, BRCA1 Protein, Chromosomal Proteins, Non-Histone, Active Transport, Cell Nucleus, Intracellular Signaling Peptides and Proteins, Terminal Repeat Sequences, Growth, Phosphoproteins, Autoimmune Diseases, DNA-Binding Proteins, Disease Models, Animal, Mice, Animals, Carrier Proteins, Tumor Suppressor p53-Binding Protein 1, DNA Damage
Chromosome Aberrations, Mice, Knockout, Genome, DNA Repair, BRCA1 Protein, Chromosomal Proteins, Non-Histone, Active Transport, Cell Nucleus, Intracellular Signaling Peptides and Proteins, Terminal Repeat Sequences, Growth, Phosphoproteins, Autoimmune Diseases, DNA-Binding Proteins, Disease Models, Animal, Mice, Animals, Carrier Proteins, Tumor Suppressor p53-Binding Protein 1, DNA Damage
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