Artículo
Homologous recombination repairs secondary replication induced DNA double-strand breaks after ionizing radiation
Autor/es | Groth, Petra
Orta Vázquez, Manuel Luis Elvers, Ingegerd Majumder, Muntasir Mamun Lagerqvist, Anne Helleday, Thomas |
Departamento | Universidad de Sevilla. Departamento de Biología Celular |
Fecha de publicación | 2012 |
Fecha de depósito | 2017-03-15 |
Publicado en |
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Resumen | Ionizing radiation (IR) produces direct two-ended DNA double-strand breaks (DSBs) primarily repaired by non-homologous end joining (NHEJ). It is, however, well established that homologous recombination (HR) is induced and ... Ionizing radiation (IR) produces direct two-ended DNA double-strand breaks (DSBs) primarily repaired by non-homologous end joining (NHEJ). It is, however, well established that homologous recombination (HR) is induced and required for repair of a subset of DSBs formed following IR. Here, we find that HR induced by IR is drastically reduced when post-DNA damage replication is inhibited in mammalian cells. Both IR-induced RAD51 foci and HR events in the hprt gene are reduced in the presence of replication polymerase inhibitor aphidicolin (APH). Interestingly, we also detect reduced IR-induced toxicity in HR deficient cells when inhibiting post-DNA damage replication. When studying DSB formation following IR exposure, we find that apart from the direct DSBs the treatment also triggers formation of secondary DSBs peaking at 7–9 h after exposure. These secondary DSBs are restricted to newly replicated DNA and abolished by inhibiting post-DNA damage replication. Further, we find that IR-induced RAD51 foci are decreased by APH only in cells replicating at the time of IR exposure, suggesting distinct differences between IR-induced HR in S- and G2-phases of the cell cycle. Altogether, our data indicate that secondary replication-associated DSBs formed following exposure to IR are major substrates for IR-induced HR repair. |
Cita | Groth, P., Orta Vázquez, M.L., Elvers, I., Majumder, M.M., Lagerqvist, A. y Helleday, T. (2012). Homologous recombination repairs secondary replication induced DNA double-strand breaks after ionizing radiation. Nucleic Acids Research, 40 (14), 6585-6594. |
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