@article {3136438,
	title = {3D genome organization contributes to genome instability at fragile sites},
	journal = {Nat Commun},
	volume = {11},
	year = {2020},
	month = {2020 Jul 17},
	pages = {3613},
	abstract = {Common fragile sites (CFSs) are regions susceptible to replication stress and are hotspots for chromosomal instability in cancer. Several features were suggested to underlie CFS instability, however, these features are prevalent across the genome. Therefore, the molecular mechanisms underlying CFS instability remain unclear. Here, we explore the transcriptional profile and DNA replication timing (RT) under mild replication stress in the context of the 3D genome organization. The results reveal a fragility signature, comprised of a TAD boundary overlapping a highly transcribed large gene with APH-induced RT-delay. This signature enables precise mapping of core fragility regions in known CFSs and identification of novel fragile sites. CFS stability may be compromised by incomplete DNA replication and repair in TAD boundaries core fragility regions leading to genomic instability. The identified fragility signature will allow for a more comprehensive mapping of CFSs and pave the way for investigating mechanisms promoting genomic instability in cancer.},
	keywords = {Aphidicolin, Cell Line, Chromatin Immunoprecipitation Sequencing, Chromosome Fragile Sites, Chromosome Mapping, DNA, DNA Replication Timing, Fibroblasts, Gene Regulatory Networks, Genome, Human, Genomic Instability, High-Throughput Nucleotide Sequencing, Humans, Neoplasms, Nucleic Acid Conformation, Sensitivity and Specificity, Transcription, Genetic},
	issn = {2041-1723},
	doi = {10.1038/s41467-020-17448-2},
	url = {https://doi.org/10.1038/s41467-020-17448-2},
	author = {Sarni, Dan and Sasaki, Takayo and Irony Tur-Sinai, Michal and Miron, Karin and Rivera-Mulia, Juan Carlos and Magnuson, Brian and Ljungman, Mats and Gilbert, David M and Kerem, Batsheva}
}
