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DTIC ADA455292: Involvement of 53BP1, a p53 Binding Protein, in Chk... |
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53BP1, a p53 binding protein, is involved in DNA damage |
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response. It is phosphorylated in response to DNA damage |
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and rapidly relocalize to sites of damage, forming |
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nuclear foci that colocalize with those formed by |
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phosphorylated histone H2AX, Mre11-Rad50-Nbs1 complex, |
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MDC1, Brca1 and other DNA damage signaling proteins. Our |
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studies aimed to determine the role of 53BP1 in DNA |
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damage response and tumor suppression. We studied the |
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function of 53BP1 in mammalian cells by knocking down |
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expression of 53BP1 using small interfering RNA (siRNA) |
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against 53BP1. We also generated 53BP1-defective |
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(53BP1tr/tr) mouse model with expression of a defective C- |
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terminal truncation of the m53BP1 protein. We have shown |
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that 53BP1 is a key transducer in the DNA damage response |
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signaling. Inhibition of 53BP1 by siRNA in human cancer |
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cell lines resulted in defective S-phase and G2/M |
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checkpoints in response to ionizing irradiation (IR). |
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53BP1 interacts with tumor suppressors p53, Chk2 and |
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Brca1, and is involved in regulation of these proteins in |
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response to IR. 53BP1tr/tr mice were growth retarded and |
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IR-sensitive. Mouse embryonic fibroblast (MEF) cells |
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generated from 53BP1tr/tr mice were hypersensitive to IR, |
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and exhibited higher level of chromosomal abnormalities |
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when treated with genotoxic stress, indicating a role of |
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53BP1 in maintaining genomic stability. Thus 53BP1 is |
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likely to play an important role in maintenance of |
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genomic stability and cancer prevention. These studies |
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allowed us gain further insights into the DNA damage |
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response pathway and the tumor suppression pathway in |
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mammalian cells. |
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Date Published: 2018-06-07 00:12:12 |
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Identifier: DTIC_ADA455292 |
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Item Size: 68803525 |
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Language: english |
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Media Type: texts |
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# Topics |
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DTIC Archive; Wang, Bin; BRIGHAM AND ... |
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@chris85 |
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