DNA repair protein Ku80 suppresses chromosomal aberrations and malignant transformation

Michael J. Difilippantonio, Jie Zhu, Hua Tang Chen, Eric Meffre, Michel C. Nussenzweig, Edward E. Max, Thomas Ried and André Nussenzweig ()
Additional contact information
Michael J. Difilippantonio: National Cancer Institute, National Institutes of Health
Jie Zhu: Experimental Immunology Branch, National Cancer Institute, National Institutes of Health
Hua Tang Chen: Experimental Immunology Branch, National Cancer Institute, National Institutes of Health
Eric Meffre: Laboratory of Molecular Immunology, and Howard Hughes Medical Institute, The Rockefeller Institute
Michel C. Nussenzweig: Laboratory of Molecular Immunology, and Howard Hughes Medical Institute, The Rockefeller Institute
Edward E. Max: Laboratory of Cell Regulation, Center for Biologics Evaluation and Research, Food and Drug Administration, National Institutes of Health
Thomas Ried: National Cancer Institute, National Institutes of Health
André Nussenzweig: Experimental Immunology Branch, National Cancer Institute, National Institutes of Health

Nature, 2000, vol. 404, issue 6777, 510-514

Abstract: Abstract Cancer susceptibility genes have been classified into two groups: gatekeepers and caretakers1. Gatekeepers are genes that control cell proliferation and death, whereas caretakers are DNA repair genes whose inactivation leads to genetic instability. Abrogation of both caretaker and gatekeeper function markedly increases cancer susceptibility. Although the importance of Ku80 in DNA double-strand break repair is well established, neither Ku80 nor other components of the non-homologous end-joining pathway are known to have a caretaker role in maintaining genomic stability. Here we show that mouse cells deficient for Ku80 display a marked increase in chromosomal aberrations, including breakage, translocations and aneuploidy. Despite the observed chromosome instabilities, Ku80-/- mice have only a slightly earlier onset of cancer2,3. Loss of p53 synergizes with Ku80 to promote tumorigenesis such that all Ku80-/-p53-/- mice succumb to disseminated pro-B-cell lymphoma before three months of age. Tumours result from a specific set of chromosomal translocations and gene amplifications involving IgH and c-Myc, reminiscent of Burkitt's lymphoma. We conclude that Ku80 is a caretaker gene that maintains the integrity of the genome by a mechanism involving the suppression of chromosomal rearrangements.

Date: 2000
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/35006670 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:404:y:2000:i:6777:d:10.1038_35006670

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/35006670

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().