FBH1 Catalyzes Regression of Stalled Replication Forks.
Cell Rep
; 10(10): 1749-1757, 2015 Mar 17.
Article
en En
| MEDLINE
| ID: mdl-25772361
ABSTRACT
DNA replication fork perturbation is a major challenge to the maintenance of genome integrity. It has been suggested that processing of stalled forks might involve fork regression, in which the fork reverses and the two nascent DNA strands anneal. Here, we show that FBH1 catalyzes regression of a model replication fork in vitro and promotes fork regression in vivo in response to replication perturbation. Cells respond to fork stalling by activating checkpoint responses requiring signaling through stress-activated protein kinases. Importantly, we show that FBH1, through its helicase activity, is required for early phosphorylation of ATM substrates such as CHK2 and CtIP as well as hyperphosphorylation of RPA. These phosphorylations occur prior to apparent DNA double-strand break formation. Furthermore, FBH1-dependent signaling promotes checkpoint control and preserves genome integrity. We propose a model whereby FBH1 promotes early checkpoint signaling by remodeling of stalled DNA replication forks.
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Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Cell Rep
Año:
2015
Tipo del documento:
Article
País de afiliación:
Dinamarca