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DNA damage response to ultra low doses of radiation

DNA damage response to ultra low doses of radiation


Insertional mutagenesis occurs when extrachromosomal DNA integrates in the host’s genome. Integration of exogenous DNA is an important factor in several therapeutic approaches, where it is regarded as either beneficial (stable restoration of a missing gene) or dangerous (insertion near an oncogene and its activation). Indeed, viral integration is considered a contributing factor in oncogenesis, even for viruses that do not encode an active integration function.

We discovered that ionizing radiation doses as low at 0.01 Gy significantly increase insertion of exogenous DNA in the genome of mammalian cells. Several of our observations challenge the intuitive explanation of the phenomenon as trapping an extrachromsomal DNA fragment during mis-repair of a genomic double-strand break by non-homologous end joining.

Importantly, we showed that that the extremely low doses of radiation also promoted the insertion of DNA from (non-integrating) viruses residing in the cells. Because the doses tested are in the range of those received by patients undergoing a computed tomography (CT) scan (10 mGy for an abdominal scan), we also performed experiments in a CT scanner and again observed the same increase in insertional mutagenesis. Given that an estimated 68 million CT scans per year are performed in the USA and the prevalence of persistent viral infections, it is of great importance to unravel the molecular mechanism of the extremely low dose induced insertional mutagenesis pathway.

Using state-of-the art genome engineering and cell biological experiments we are unraveling the molecular mechanism of this novel DNA damage response mechanism.

Relevant publications

In preparation.