Radiation-Induced Chromosomal Breaks may be DNA Repair Fragile Sites with Larger-scale Correlations to Eight Double-Strand-Break Related Data Sets over the Human Genome.

In this work, we compared the genomic distribution of common radiation-induced chromosomal breaks to eight different data sets covering the whole human genome. Sites with a high probability of chromatid breakage after exposure to low and high ionization density radiations were often located inside common and rare fragile sites, indicating that they may be a new and more local type of DNA repair-related fragility. Breaks in specific chromosome bands after acute exposure to oil and benzene also showed strong correlation with these sites and fragile sites. In addition, close correlation was found with cytologically detected chiasma and MLH1 immunofluorescence sites and with the HapMap recombination density distributions. Also, of interest, copy number changes occurred predominantly at radiation-induced breaks and fragile sites, at least for breast cancers with poor prognosis, and they decreased weakly but significantly in regions with increasing recombination and CpG density. An increased CpG density is linked to regions of high gene density to secure high-fidelity reproduction and survival. To minimize cancer induction, cancer-related genes are often located in regions of decreased recombination density and/or higher-than-average CpG density. It is compelling that all these data sets were influenced by the cells' handling of double-strand breaks and, more generally, DNA damage on its genome. In fact, the DNA repair genes systematically avoid regions with a high recombination density, as they need to be intact to accurately handle repairable DNA lesions.