FBH1 promotes DNA double-strand breakage and apoptosis in response to DNA replication stress.
J Cell Biol
; 200(2): 141-9, 2013 Jan 21.
Article
em En
| MEDLINE
| ID: mdl-23319600
ABSTRACT
Proper resolution of stalled replication forks is essential for genome stability. Purification of FBH1, a UvrD DNA helicase, identified a physical interaction with replication protein A (RPA), the major cellular single-stranded DNA (ssDNA)-binding protein complex. Compared with control cells, FBH1-depleted cells responded to replication stress with considerably fewer double-strand breaks (DSBs), a dramatic reduction in the activation of ATM and DNA-PK and phosphorylation of RPA2 and p53, and a significantly increased rate of survival. A minor decrease in ssDNA levels was also observed. All these phenotypes were rescued by wild-type FBH1, but not a FBH1 mutant lacking helicase activity. FBH1 depletion had no effect on other forms of genotoxic stress in which DSBs form by means that do not require ssDNA intermediates. In response to catastrophic genotoxic stress, apoptosis prevents the persistence and propagation of DNA lesions. Our findings show that FBH1 helicase activity is required for the efficient induction of DSBs and apoptosis specifically in response to DNA replication stress.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Estresse Fisiológico
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Apoptose
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DNA Helicases
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Proteínas de Ligação a DNA
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Replicação do DNA
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Quebras de DNA de Cadeia Dupla
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article