¹²⁵I Decay in Microorganisms: A Prokaryotic Model System for Examining the Role of Unrepaired Double-Strand DNA Breaks in Cell Killing

Abstract

Iodine-125, when incorporated into the DNA of microorganisms as iododeoxyuridine, has been demonstrated to induce double-strand DNA breaks (DSBs) with approximately 100% efficiency when it undergoes radioactive decay. In the biological dose range approximately 2/3 of these breaks are repaired in a wild type (rec⁺) strain of E. coli K12, but none are repaired in the corresponding recombination deficient (recA) strain. Each unrepaired DSB appears to produce a lethal event in either strain. Survival experiments imply that maximum repair of DSBs in rec⁺ cells can occur in the presence of only a single genome per cell and therefore does not require a recombi-national event. However, experiments with ¹²⁵I-labelled small intracellular closed circular DNA mulecules (super-infecting phage λ, MW=33×10⁶d) demonstrate no repair of decay-induced DSBs, suggesting that the superstructure of the large cellular chromosome plays an important role in the repair of DSBs, even in the absence of recombination.