Double strand break metabolism and cancer susceptibility: lessons from the mre11 complex.
Cell Cycle
; 3(5): 541-2, 2004 May.
Article
em En
| MEDLINE
| ID: mdl-15034299
ABSTRACT
Hypomorphic mutants affecting the Mre11 complex components Mre11 (Mre11(ATLD1/ATLD1)) and Nbs1 (Nbs1(DeltaB/DeltaB)) have been established in the mouse. These mutations recapitulate those inherited in human chromosome fragility syndromes, the ataxia-telangiectasia like disorder and Nijmegen breakage syndrome. At the cellular level, the human and murine mutants exhibit defects in the intra S and G2/M checkpoints and marked chromosome instability. Whereas these outcomes are associated with predisposition to malignancy in humans, similar predisposition was not observed in either Mre11(ATLD1/ATLD1) or Nbs1(DeltaB/DeltaB) mice. These data demonstrate that chromosome breakage per se is insufficient to significantly enhance the initiation of tumorigenesis. However, these mutations greatly enhanced the risk of malignancy in p53+/- mice. We propose that proper metabolism of chromosome breaks arising during DNA replication is uniquely important for suppressing loss of heterozygosity and thus the penetrance of recessive oncogenic lesions.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Dano ao DNA
/
Ciclo Celular
/
Neoplasias
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article