Ku80 deletion suppresses spontaneous tumors and induces a p53-mediated DNA damage response.

Holcomb, Valerie B; Rodier, Francis; Choi, YongJun; Busuttil, Rita A; Vogel, Hannes; Vijg, Jan; Campisi, Judith; Hasty, Paul · Cancer Res · 2008

basic_science · Level V

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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.

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