Molecular and Cellular Responses to Ionization Radiation in Untransformed Fibroblasts from the Rothmund–Thomson Syndrome: Influence of the Nucleo-Shuttling of the ATM Protein Kinase

The Rothmund–Thomson syndrome (RTS) is a rare autosomal recessive disease associated with poikiloderma, telangiectasias, sun-sensitive rash, hair growth problems, juvenile cataracts and, for subset of some RTS patients, high risk cancer, especially osteosarcoma. Most the cases are caused by biallelic mutations RECQL4 gene, coding DNA helicase that belongs to RecQ family. Cellular and post-radiotherapy radiosensitivity was reported in cells patients since 1980s. However, molecular basis this particular phenotype has not been documented reliably link biological clinical responses ionizing radiation (IR) from patients. aim study therefore document specificities examining radiation-induced nucleo-shuttling ATM (RIANS) recognition repair double-strand breaks (DSB) three skin fibroblasts cell lines derived two patients’ parents. results showed tested were moderate but significant radiosensitivity, yield micronuclei, impaired DSB normal at 24 h likely delayed RIANS, supported sequestration proteins overexpressed cytoplasm. To our knowledge, report first radiobiological characterization both cellular scales.