Your browser doesn't support javascript.
loading
Persistently stalled replication forks inhibit nucleotide excision repair in trans by sequestering Replication protein A.
Tsaalbi-Shtylik, Anastasia; Moser, Jill; Mullenders, Leon H F; Jansen, Jacob G; de Wind, Niels.
Afiliação
  • Tsaalbi-Shtylik A; Department of Toxicogenetics, Leiden University Medical Center, PO box 9600, 2300 RC Leiden, The Netherlands.
Nucleic Acids Res ; 42(7): 4406-13, 2014 Apr.
Article em En | MEDLINE | ID: mdl-24464993
Rev3, the catalytic subunit of DNA polymerase ζ, is essential for translesion synthesis of cytotoxic DNA photolesions, whereas the Rev1 protein plays a noncatalytic role in translesion synthesis. Here, we reveal that mammalian Rev3(-/-) and Rev1(-/-) cell lines additionally display a nucleotide excision repair (NER) defect, specifically during S phase. This defect is correlated with the normal recruitment but protracted persistence at DNA damage sites of factors involved in an early stage of NER, while repair synthesis is affected. Remarkably, the NER defect becomes apparent only at 2 h post-irradiation indicating that Rev3 affects repair synthesis only indirectly, rather than performing an enzymatic role in NER. We provide evidence that the NER defect is caused by scarceness of Replication protein A (Rpa) available to NER, resulting from its sequestration at stalled replication forks. Also the induction of replicative stress using hydroxyurea precludes the accumulation of Rpa at photolesion sites, both in Rev3(-/-) and in wild-type cells. These data support a model in which the limited Rpa pool coordinates replicative stress and NER, resulting in increased cytotoxicity of ultraviolet light when replicative stress exceeds a threshold.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Reparo do DNA / Replicação do DNA / Proteína de Replicação A Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2014 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Reparo do DNA / Replicação do DNA / Proteína de Replicação A Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2014 Tipo de documento: Article