Role for the BRCA1 C-terminal repeats (BRCT) protein 53BP1 in maintaining genomic stability - PubMed (original) (raw)

. 2003 Apr 25;278(17):14971-7.

doi: 10.1074/jbc.M212484200. Epub 2003 Feb 10.

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• PMID: 12578828
• DOI: 10.1074/jbc.M212484200

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Role for the BRCA1 C-terminal repeats (BRCT) protein 53BP1 in maintaining genomic stability

Julio C Morales et al. J Biol Chem. 2003.

Free article

Abstract

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.

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