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Cancer Res. 2008 Nov 15;68(22):9497-502. doi: 10.1158/0008-5472.CAN-08-2085.

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

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  • 1Department of Molecular Medicine, Institute of Biotechnology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78245-3207, USA.

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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