Sensitivity of DNA double-strand break loci is coupled with spatial interaction density of chromatin

Abstract Background: DNA double-strand breaks, one of the most serious types of damage to the genome, are closely related to chromatin rearrangement and oncogene activation. However, the mechanisms of DSB formation and repair upon the genome are still unclear. Recent advances in chromatin conformation capture technology Hi-C enable clear identification of the relationship between chromatin 3D structure and DSBs. Nonetheless, how to interpret this relationship, especially the contribution to DSB formation at the level of TAD, remains poorly understood. Results: Here, we classify the collected DSB data for systematic identification and annotation of these DSB loci from a multi-omics perspective, and construct a systematic framework for studying DSBs. In addition, we propose a model for TAD Density. TAD Density can well characterize the relationship between different TAD internal interaction densities and DSB occurrence. The dynamic changes of TAD Density tend to be associated with the enrichment of fragile regions of the genome or even essential genes. This relationship was explained by the ancient Chinese mythology “Journey to the West”. Furthermore, with TAD Density, we screened for genes associated with prognosis of tumor patients. Conclusions: In conclusion, our study systematically compared and annotated DSB loci in terms of sequence features, epigenetic modifications, and the three-dimensional structure of chromatin. While validating the general pattern of DSBs, we propose a mechanism for chromatin interaction density within TAD to protect the genome from DSB damage.