rdf:type |
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lifeskim:mentions |
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pubmed:issue |
17
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pubmed:dateCreated |
2003-4-21
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pubmed: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.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
|
pubmed:status |
MEDLINE
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pubmed:month |
Apr
|
pubmed:issn |
0021-9258
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pubmed:author |
|
pubmed:issnType |
Print
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pubmed:day |
25
|
pubmed:volume |
278
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
14971-7
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:12578828-Active Transport, Cell Nucleus,
pubmed-meshheading:12578828-Animals,
pubmed-meshheading:12578828-Autoimmune Diseases,
pubmed-meshheading:12578828-BRCA1 Protein,
pubmed-meshheading:12578828-Carrier Proteins,
pubmed-meshheading:12578828-Chromosomal Proteins, Non-Histone,
pubmed-meshheading:12578828-Chromosome Aberrations,
pubmed-meshheading:12578828-DNA Damage,
pubmed-meshheading:12578828-DNA Repair,
pubmed-meshheading:12578828-DNA-Binding Proteins,
pubmed-meshheading:12578828-Disease Models, Animal,
pubmed-meshheading:12578828-Genome,
pubmed-meshheading:12578828-Growth,
pubmed-meshheading:12578828-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:12578828-Mice,
pubmed-meshheading:12578828-Mice, Knockout,
pubmed-meshheading:12578828-Phosphoproteins,
pubmed-meshheading:12578828-Terminal Repeat Sequences
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pubmed:year |
2003
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pubmed:articleTitle |
Role for the BRCA1 C-terminal repeats (BRCT) protein 53BP1 in maintaining genomic stability.
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pubmed:affiliation |
Department of Biochemistry and Molecular Biology, University of Texas Health Sciences Center, Houston, Texas 77030, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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