Polμ deficiency induces moderate shortening of P53−/− mouse lifespan and modifies tumor spectrum

Publication date: Available online 10 April 2017
Source:DNA Repair
Author(s): Beatriz Escudero, Diego Herrero, Yaima Torres, Susana Cañón, Antonio Molina, Rosa M. Carmona, Javier Suela, Luis Blanco, Enrique Samper, Antonio Bernad
Non-homologous end joining (NHEJ) is the main mechanism for double strand break (DSB) DNA repair. The error-prone DNA polymerase mu (Polμ) is involved in immunoglobulin variable region rearrangement and in general, NHEJ in non-lymphoid cells. Deletion of NHEJ factors in P53^−/− mice, which are highly prone to development of T cell lymphoma, generally increases cancer incidence and shifts the tumor spectrum towards aggressive pro-B lymphoma. In contrast, Polμ deletion increased sarcoma incidence, proportionally reducing pro-B lymphoma development on the P53-deficient background. Array comparative genomic hybridization (aCGH) analyses showed DNA copy number alterations in both P53^−/− and Polμ^−/−P53^−/− lymphomas. Our results also indicate that the increase in sarcoma incidence in Polμ^−/−P53^−/− mice could be associated with Cdk4 and Kub3 amplification and overexpression. These results identify a role for Polμ in the prevention of sarcomagenesis on a murine P53-deficient background, in contrast to most other NHEJ factors.



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