Replication stress and cancer: it takes two to tango.
Exp Cell Res
; 329(1): 26-34, 2014 Nov 15.
Article
em En
| MEDLINE
| ID: mdl-25257608
ABSTRACT
Problems arising during DNA replication require the activation of the ATR-CHK1 pathway to ensure the stabilization and repair of the forks, and to prevent the entry into mitosis with unreplicated genomes. Whereas the pathway is essential at the cellular level, limiting its activity is particularly detrimental for some cancer cells. Here we review the links between replication stress (RS) and cancer, which provide a rationale for the use of ATR and Chk1 inhibitors in chemotherapy. First, we describe how the activation of oncogene-induced RS promotes genome rearrangements and chromosome instability, both of which could potentially fuel carcinogenesis. Next, we review the various pathways that contribute to the suppression of RS, and how mutations in these components lead to increased cancer incidence and/or accelerated ageing. Finally, we summarize the evidence showing that tumors with high levels of RS are dependent on a proficient RS-response, and therefore vulnerable to ATR or Chk1 inhibitors.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Rearranjo Gênico
/
Instabilidade Cromossômica
/
Replicação do DNA
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Neoplasias
Limite:
Humans
Idioma:
En
Revista:
Exp Cell Res
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Espanha