Complex genomic patterns of abasic sites in mammalian DNA revealed by a high-resolution SSiNGLe-AP method

• Published in: Nature communications Vol. 13; no. 1; pp. 5868 - 21
• Main Authors: Cai, Ye, Cao, Huifen, Wang, Fang, Zhang, Yufei, Kapranov, Philipp
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05.10.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 45/23; 45/91; 631/136/7; 631/1647/2217; 631/337/1427; Animal tissues; Animals; Damage patterns; Deoxyribonucleic acid; DNA; DNA - genetics; DNA - metabolism; DNA damage; DNA Damage - genetics; DNA Repair; Gene expression; Genomes; Genomics; High resolution; Humanities and Social Sciences; Humans; Lesions; Mammals; Mammals - genetics; Mice; multidisciplinary; Nucleotides; Nucleotides - genetics; Science; Science (multidisciplinary); Tumor cell lines
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-33594-1

DNA damage plays a critical role in biology and diseases; however, how different types of DNA lesions affect cellular functions is far from clear mostly due to the paucity of high-resolution methods that can map their locations in complex genomes, such as those of mammals. Here, we present the development and validation of SSiNGLe-AP method, which can map a common type of DNA damage, abasic (AP) sites, in a genome-wide and high-resolution manner. We apply this method to six different tissues of mice with different ages and human cancer cell lines. We find a nonrandom distribution of AP sites in the mammalian genome that exhibits dynamic enrichment at specific genomic locations, including single-nucleotide hotspots, and is significantly influenced by gene expression, age and tissue type in particular. Overall, these results suggest that we are only starting to understand the true complexities in the genomic patterns of DNA damage. Abasic (AP) sites represent a prominent type of DNA damage, yet the genomics of this lesion remains unexplored. Here, the authors report a method to map such sites at the nucleotide level in complex genomes and use it to extract complex age- and tissue-dependent patterns of AP sites in mammals.