© 2015 Elsevier B.V. Fanconi anemia (FA) is a rare, clinically heterogeneous autosomal recessive or X-linked genetic disease characterized by chromosome fragility, congenital malformations and cancer susceptibility. FA patients are usually radiosensitive when exposed to radiotherapy but the role of the FA in response to ionizing radiation (IR) is controversial. Here we have investigated IR-induced activation of the FA pathway by systematically analyzing monoubiquitination of the central protein FANCD2 and subsequent recruitment to stalled replication forks in primary fibroblasts. We developed an immunolabelling method to simultaneously visualize IR-induced FANCD2 and γH2AX foci in S-phase. We observed FANCD2 foci formation in a subset of IR-induced γH2AX foci in S-phase cells. This was observed at doses of IR ranging from 0.1 to 5.0. Gy in a dose dependent non-threshold fashion. Our results indicate that minimum doses of IR can produce replication fork stalling and FA pathway activation during S-phase in primary cells.
|Journal||Mutation Research - Genetic Toxicology and Environmental Mutagenesis|
|Publication status||Published - 1 Nov 2015|
- DNA damage response
- Fanconi anemia
- Ionizing radiation