title: Ku80 deletion suppresses spontaneous tumors and induces a p53-mediated DNA damage response.
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.
authors.affiliation: Department of Molecular Medicine, Institute of Biotechnology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78245-3207, USA.
authors.forename: Valerie B
authors.initials: VB
authors.lastname: Holcomb
authors.forename: Francis
authors.initials: F
authors.lastname: Rodier
authors.forename: YongJun
authors.initials: Y
authors.lastname: Choi
authors.forename: Rita A
authors.initials: RA
authors.lastname: Busuttil
authors.forename: Hannes
authors.initials: H
authors.lastname: Vogel
authors.forename: Jan
authors.initials: J
authors.lastname: Vijg
authors.forename: Judith
authors.initials: J
authors.lastname: Campisi
authors.forename: Paul
authors.initials: P
authors.lastname: Hasty
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000502:physiology*; D002869:Chromosome Aberrations; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000032:analysis; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000502:physiology*; D017491:Genes, APC; D007421:Intestine, Small / Q000378:metabolism; D000072200:Ku Autoantigen; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000517:prevention & control*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
chemical_list: D034961:Antigens, Nuclear; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; C000606510:Xrcc6 protein, mouse; D000072200:Ku Autoantigen