PT  - JOURNAL ARTICLE
AU  - Katsushi Kagaya
AU  - Naoto Noma
AU  - Io Yamamoto
AU  - Sanki Tashiro
AU  - Fuyuki Ishikawa
AU  - Makoto T Hayashi
TI  - A Single Defined Sister Chromatid Fusion Destabilizes Cell Cycle through Micronuclei Formation
AID  - 10.1101/607341
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 607341
4099  - http://biorxiv.org/content/early/2019/04/12/607341.short
4100  - http://biorxiv.org/content/early/2019/04/12/607341.full
AB  - Chromosome fusion is deleterious among oncogenic chromosome rearrangements, and has been proposed to cause multiple tumor-driving abnormalities. Conventional methodologies, however, lack the strictness of the experimental controls on the fusion such as the exact timing, the number and the types of fusion in a given cell. Here, we developed a human cell-based sister chromatid fusion visualization system (FuVis), in which a single defined sister chromatid fusion is induced by CRISPR/Cas9 concomitantly with mCitrine expression. Fused chromosome developed numerical and structural abnormalities, including chromosome fragmentation, an indicative of eventual chromothripsis. Live cell imaging and hierarchical Bayesian modeling indicated that micronucleus (MN) is generated in the first few cell cycle, and that cells with MN tend to possess cell cycle abnormalities. These results demonstrate that, although most cells can tolerate a single fusion, even a single sister chromatid fusion destabilizes cell cycle through MN formation.