This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Holcomb, V. B. Articles by Hasty, P. Search for Related Content PubMed PubMed Citation Articles by Holcomb, V. B. Articles by Hasty, P.

Ku80 Deletion Suppresses Spontaneous Tumors and Induces a p53-Mediated DNA Damage Response

¹ Department of Molecular Medicine, Institute of Biotechnology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas; ² Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California; ³ Buck Institute for Age Research, Novato, California; ⁴ Department of Pathology, Stanford University Medical Center, Palo Alto, California; and ⁵ Albert Einstein College of Medicine, Bronx, New York

Requests for reprints: Paul Hasty, The University of Texas Health Science Center at San Antonio, 15355 Lambda Drive, San Antonio, TX 78245-3207. Phone: 210-567-7278; Fax: 210-567-7247; E-mail: hastye{at}uthscsa.edu.

Key Words: DNA repair • mouse cancer models • NHEJ

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. [Cancer Res 2008;68(22):9497–502]