title: Radiation-generated short DNA fragments may perturb non-homologous end-joining and induce genomic instability.
abstract: 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.
authors.affiliation: Department of Radiation Medicine, Georgetown University Medical Center, USA.
authors.forename: Dalong
authors.initials: D
authors.lastname: Pang
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Winters
authors.forename: Mira
authors.initials: M
authors.lastname: Jung
authors.forename: Shubhadeep
authors.initials: S
authors.lastname: Purkayastha
authors.forename: Luciane R
authors.initials: LR
authors.lastname: Cavalli
authors.forename: Sergey
authors.initials: S
authors.lastname: Chasovkikh
authors.forename: Bassem R
authors.initials: BR
authors.lastname: Haddad
authors.forename: Anatoly
authors.initials: A
authors.lastname: Dritschilo
mesh_terms: D000818:Animals; D004247:DNA / Q000235:genetics* / Q000528:radiation effects*; D053938:DNA Fragmentation / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D042822:Genomic Instability / Q000235:genetics* / Q000528:radiation effects*; D006801:Humans; D009154:Mutation / Q000235:genetics* / Q000528:radiation effects*; D011829:Radiation Dosage
chemical_list: D004247:DNA