Ionizing radiation-induced fragmentation of plasmid DNA - Atomic force microscopy and biophysical modeling

It is widely accepted that DNA double-strand breaks (DSBs) are closely correlated with radiation-induced cell killing and are the most critical lesions related to cellular endpoints like mutagenesis and transformation. High linear energy transfer (LET) radiation produces more severe and complex damage due to the fact that induced DSBs are not randomly distributed but clustered at different levels of DNA organization. In this paper, direct visualization of DSBs induced in a plasmid supercoiled DNA by low- and high-LET radiation is presented. Resulting DNA fragments distributions obtained by use of atomic force microscopy (AFM) are shown. Moreover, a biophysical model of spatially correlated DSBs formation in the framework of the Local Effect Model (LEM) is introduced and its predictions on DNA fragment formation are discussed.