Details

Autor(en) / Beteiligte

• WOO, Y
• WRIGHT, S. M
• BRONSON, R. T
• MORSE, H. C
• ROOPENIAN, D
• MILLS, K. D
• MAAS, S. A
• ALLEY, T. L
• CADDLE, L. B
• KAMDAR, S
• AFFOURTIT, J
• FOREMAN, O
• AKESON, E. C
• SHAFFER, D

Titel

The nonhomologous end joining factor Artemis suppresses multi-tissue tumor formation and prevents loss of heterozygosity

Ist Teil von

• Oncogene, 2007-09, Vol.26 (41), p.6010-6020

Ort / Verlag

Basingstoke: Nature Publishing

Erscheinungsjahr

2007

Quelle

MEDLINE

Beschreibungen/Notizen

• Nonhomologous end joining (NHEJ) is a critical DNA repair pathway, with proposed tumor suppression functions in many tissues. Mutations in the NHEJ factor ARTEMIS cause radiation-sensitive severe combined immunodeficiency in humans and may increase susceptibility to lymphoma in some settings. We now report that deficiency for Artemis (encoded by Dclre1c/Art in mouse) accelerates tumorigenesis in several tissues in a Trp53 heterozygous setting, revealing tumor suppression roles for NHEJ in lymphoid and non-lymphoid cells. We also show that B-lineage lymphomas in these mice undergo loss of Trp53 heterozygosity by allele replacement, but arise by mechanisms distinct from those in Art Trp53 double null mice. These findings demonstrate a general tumor suppression function for NHEJ, and reveal that interplay between NHEJ and Trp53 loss of heterozygosity influences the sequence of multi-hit oncogenesis. We present a model where p53 status at the time of tumor initiation is a key determinant of subsequent oncogenic mechanisms. Because Art deficient mice represent a model for radiation-sensitive severe combined immunodeficiency, our findings suggest that these patients may be at risk for both lymphoid and non-lymphoid cancers.