Analysis of deletions induced in the genome of mammalian cells by ionizing radiation.
A theory is presented for the distribution in size of deletions induced by ionizing radiation, based on three assumptions: (1) deletions that are observed delete part or all of a gene to make a mutation, but not adjacent DNA sequences essential for survival of the mutant; (2) deletions are distributed at random along the DNA; (3) the probability of formation is proportional to the rate at which the two endpoints, which must meet to form the deletion, collide with each other. Experimental data for radiation-induced deletions in human and hamster hprt genes are in good agreement with calculations that assume the inducing lesion does not break the intracellular chromatin fiber; calculations assuming the inducing lesion is a break are not a good fit to the data. The low frequency of deletions observed in the hamster aprt gene is shown to be a consequence of the small gene size and the presence of a nearby essential DNA sequence, ensuring that most deletions affecting the gene also delete the essential sequence and are thus not observed.
D000228:Adenine Phosphoribosyltransferase / Q000235:genetics; D000818:Animals; D002843:Chromatin / Q000528:radiation effects; D006224:Cricetinae; D004249:DNA Damage; D005796:Genes / Q000528:radiation effects*; D016678:Genome; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D008957:Models, Genetic; D016296:Mutagenesis; D011839:Radiation, Ionizing; D017384:Sequence Deletion
D002843:Chromatin; D000228:Adenine Phosphoribosyltransferase; D007041:Hypoxanthine Phosphoribosyltransferase