Radiation-generated short DNA fragments may perturb non-homologous end-joining and induce genomic instability

Cells exposed to densely ionizing radiation (high-let) experience more severe biological damage than do cells exposed to sparsely ionizing radiation (low-let). the prevailing hypothesis is that high-let radiations induce dna double strand-breaks (dsb) that are more complex and clustered,and are thereby more challenging to repair. here,we present experimental data obtained by atomic force microscopy imaging,dna-dependent protein kinase (dna-pk) activity determination,dna ligation assays,and genomic studies to suggest that short dna fragments are important products of radiation-induced dna lesions,and that the lengths of dna fragments may be significant in the cellular responses to ionizing radiation. we propose the presence of a subset of short dna fragments that may affect cell survival and genetic stability following exposure to ionizing radiation,and that the enhanced biological effects of high-let radiation may be explained,in part,by the production of increased quantities of short dna fragments.