2026-09-23 理化学研究所,神戸大学,科学技術振興機構
1細胞解析による複数の新たな染色体脆弱部位の同定
＜関連情報＞
- https://www.riken.jp/press/2026/20260923_1/index.html
- https://www.nature.com/articles/s41467-026-76451-1
染色体切断の単一細胞マッピングにより、異なるDNA複製タイミング特性を持つ複数の脆弱部位クラスが特定された Single-cell mapping of chromosome breaks identifies multiple fragile site classes with distinct DNA replication timing landscapes
Jothivanan Elumalai & Ichiro Hiratani
Nature Communications Published:23 September 2026
DOI:https://doi.org/10.1038/s41467-026-76451-1
Abstract
Common fragile sites (CFSs) are genomic regions susceptible to chromosome breaks. However, because they were identified using cell populations, low-frequency fragile sites (non-CFSs) could have been overlooked. Here we perform single-cell genome-wide mapping and classification of aphidicolin-induced chromosome breaks. In human osteosarcoma cells, 42% of breaks exhibit features of CFSs. The remaining 58% are non-CFSs that are ‘rare’ and replicate throughout the S-phase. Among non-CFSs, we identify early-S replicating breaks associated with transcription-replication conflicts, as well as two additional break classes. One is dependent on transcription and coincides with early-to-late-S replication timing (RT) transition regions, while another class exhibits late-S RT with its frequency increasing upon transcription inhibition. Intriguingly, we find that different RT landscapes are associated with distinct aphidicolin-induced RT behavior and break classes. Our data reveal the frequencies, RT landscapes, and mechanistic differences among distinct break classes, providing a comprehensive view of genomic regions prone to breakage under replication stress.
