Polµ deficiency induces moderate shortening of P53-/- mouse lifespan and modifies tumor spectrum.
DNA Repair (Amst)
; 54: 40-45, 2017 06.
Article
em En
| MEDLINE
| ID: mdl-28460268
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 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.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Sarcoma
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Proteína Supressora de Tumor p53
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DNA Polimerase Dirigida por DNA
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Reparo do DNA por Junção de Extremidades
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Carcinogênese
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
DNA Repair (Amst)
Assunto da revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Espanha