Abstract
About 45% of the human genome is composed of transposable elements. In which, LINE-1 (long interspersed nucleotide element-1) is most abundant components, comprising around 17% of whole genome. In human cells, ~100 copies of LINE-1 are retrotransposition-competent, and the action of LINE-1 thought to be a driving force of evolution and human genetic diversity. Because the random insertion of LINE-1 could disrupt the gene structure and alter the expression profile of cellular transcription, the association of LINE-1 activities and cancer development were strongly suggested.
Current studies show the induction of LINE-1 retrotranspositon following the exposure to genotoxic reagent, such as ionizing radiation. Moreover, this phenomenon is dependent on the ATM kinase activity, which is a critical protein kinase in DNA damage response.
In this study, we used a reporter for accessing the frequency of LINE-1 retrotransposition, and homing-endonuclease to produce the DNA double strand breaks (DSB) (utilization of these nucleases enable us to exclude the side effects of radiation exposure). Induction of DSB by these nucleases show the significant increase of LINE-1 retrotransposition in several cell lines. Furthermore, this assay system gives the information about the integration site of LINE-1, I would refer to the preference of these integration site of LINE-1.
At this time, we investigate the function of ATM in the regulation of LINE-1 retrotransposition, and found the association of LINE-1 proteins with ATM signaling pathway. I would like to discuss the functional link between chromosomal instability induced by radiation exposure and LINE-1 retrotransposion.
