Fanconi anemia proteins stabilize replication forks.
DNA Repair (Amst)
; 7(12): 1973-81, 2008 Dec 01.
Article
em En
| MEDLINE
| ID: mdl-18786657
ABSTRACT
Fanconi anemia (FA) is a recessive genetic disorder characterized by hypersensitivity to crosslinking agents that has been attributed to defects in DNA repair and/or replication. FANCD2 and the FA core complex bind to chromatin during DNA replication; however, the role of FA proteins during replication is unknown. Using Xenopus cell-free extracts, we show that FANCL depletion results in defective DNA replication restart following treatment with camptothecin, a drug that results in DSBs during DNA replication. This defect is more pronounced following treatment with mitomycin C, presumably because of an additional role of the FA pathway in DNA crosslink repair. Moreover, we show that chromatin binding of FA core complex proteins during DNA replication follows origin assembly and origin firing and is dependent on the binding of RPA to ssDNA while FANCD2 additionally requires ATR, consistent with FA proteins acting at replication forks. Together, our data suggest that FA proteins play a role in replication restart at collapsed replication forks.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Cromatina
/
Replicação do DNA
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Proteína do Grupo de Complementação L da Anemia de Fanconi
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Proteína do Grupo de Complementação D2 da Anemia de Fanconi
Limite:
Animals
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article