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Updated: Jun 20, 2026

Capturing Common Fragile Site Breaks by Native γH2A.X ChIP
Published on: January 24, 2025
Early replication fragile sites are associated with cancer-related CNVs and SNVs in human embryonic stem cells
Yu-Ping Dong1, Menglin Qiu2, Haoyu Tang2
1State Key Laboratory of Genetic Evolution & Animal Models, Key Laboratory of Animal Models and Human Disease Mechanisms of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650201, China; University of Chinese Academy of Sciences, Beijing 101408, China.
Abstract:
Long-term culture of human embryonic stem cells (hESCs) often induces chromosomal abnormalities, which limits their clinical use. However, the underlying mechanisms are unclear. Early replication fragile sites (ERFSs) are genomic loci susceptible to breakage in early S-phase and serve as hotspots for chromosomal rearrangements, with established links to carcinogenesis. To map ERFSs in hESCs, we established the early S-phase synchronization protocols and identified ERFSs. These ERFSs are enriched in GC content and short interspersed nuclear elements (SINEs) and are frequently located in promoters or enhancers of genes involved in pluripotency, proliferation, and genomic stability. ERFSs also overlap with regions associated with copy number variants (CNVs) and single nucleotide variants (SNVs) linked to cancers. Furthermore, we found that chromatin accessibility contributes to ERFS formation. Collectively, these findings provide a key resource for advancing ERFS research, offering insights into the phenotypic and genomic alterations observed in long-term hESC cultures.
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