Relevancia de la vía de Fanconi en el copiado de ADN dañado por luz UV

Here we show that irradiation with low doses of UV light causes modest accumulation of replication-coupled double strand breaks (DSBs), i.e. collapsed forks. Remarkably, the Fanconi Anemia protein FANCD2 is central to prevent the aberrant processing of UV-triggered DSBs and the generation of micronu...

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Detalles Bibliográficos
Autor principal: Federico, María Belén
Otros Autores: Carballo, Marta
Formato: Tesis doctoral acceptedVersion
Lenguaje:Español
Publicado: Facultad de Farmacia y Bioquímica 2016
Materias:
UV
ADN
Acceso en línea:http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_1387
http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_1387.dir/1387.PDF
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Sumario:Here we show that irradiation with low doses of UV light causes modest accumulation of replication-coupled double strand breaks (DSBs), i.e. collapsed forks. Remarkably, the Fanconi Anemia protein FANCD2 is central to prevent the aberrant processing of UV-triggered DSBs and the generation of micronuclei and chromosome fusions but is dispensable to modulate cell death. Specifically, FANCD2 promotes homologous recombination-dependent repair of UV-triggered DSBs, thus preventing their aberrant processing by non-homologous end joining. Hence, the homologous recombination-dependent tumor suppressor function of FANCD2 is not restricted to inter-strand crosslinks but instead applies to replication-coupled DSBs that arise from a broader range of genotoxic stimuli.