Ku80 deletion suppresses spontaneous tumors and induces a p53-mediated DNA damage response.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 19010925.
- Also identified by DOI 10.1158/0008-5472.CAN-08-2085 and PMC identifier 4034752.
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Abstract
Ku80 facilitates DNA repair and therefore should suppress cancer. However, ku80(-/-) mice exhibit reduced cancer, although they age prematurely and have a shortened life span. We tested the hypothesis that Ku80 deletion suppresses cancer by enhancing cellular tumor-suppressive responses to inefficiently repaired DNA damage. In support of this hypothesis, Ku80 deletion ameliorated tumor burden in APC(MIN) mice and increased a p53-mediated DNA damage response, DNA lesions, and chromosomal rearrangements. Thus, contrary to its assumed role as a caretaker tumor suppressor, Ku80 facilitates tumor growth most likely by dampening baseline cellular DNA damage responses.
Medical subject headings
- Antigens, Nuclear
- DNA Damage
- DNA-Binding Proteins
- Neoplasms
- Tumor Suppressor Protein p53