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

Valerie B. Holcomb, Francis Rodier, Yongjun Choi, Rita A. Busuttil, Hannes Vogel, Jan Vijg, Judith Campisi, Paul Hasty

Research output: Contribution to journalArticle

20 Scopus citations

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 APCMIN 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.

Original languageEnglish (US)
Pages (from-to)9497-9502
Number of pages6
JournalCancer Research
Volume68
Issue number22
DOIs
StatePublished - Nov 15 2008

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Holcomb, V. B., Rodier, F., Choi, Y., Busuttil, R. A., Vogel, H., Vijg, J., Campisi, J., & Hasty, P. (2008). Ku80 deletion suppresses spontaneous tumors and induces a p53-mediated DNA damage response. Cancer Research, 68(22), 9497-9502. https://doi.org/10.1158/0008-5472.CAN-08-2085