Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5510951 | DNA Repair | 2017 | 6 Pages |
Abstract
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 P53â/â 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 P53â/â and Polμâ/âP53â/â lymphomas. Our results also indicate that the increase in sarcoma incidence in Polμâ/âP53â/â 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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Authors
Beatriz Escudero, Diego Herrero, Yaima Torres, Susana Cañón, Antonio Molina, Rosa M. Carmona, Javier Suela, Luis Blanco, Enrique Samper, Antonio Bernad,