PT  - JOURNAL ARTICLE
AU  - Katsushi Kagaya
AU  - Naoto Noma-Takayasu
AU  - Io Yamamoto
AU  - Sanki Tashiro
AU  - Fuyuki Ishikawa
AU  - Makoto T Hayashi
TI  - Chromosome instability induced by a single defined sister chromatid fusion
AID  - 10.26508/lsa.202000911
DP  - 2020 Dec 01
TA  - Life Science Alliance
PG  - e202000911
VI  - 3
IP  - 12
4099  - https://www.life-science-alliance.org/content/3/12/e202000911.short
4100  - https://www.life-science-alliance.org/content/3/12/e202000911.full
SO  - Life Sci. Alliance2020 Dec 01; 3
AB  - Chromosome fusion is a frequent intermediate in oncogenic chromosome rearrangements and has been proposed to cause multiple tumor-driving abnormalities. In conventional experimental systems, however, these abnormalities were often induced by randomly induced chromosome fusions involving multiple different chromosomes. It was therefore not well understood whether a single defined type of chromosome fusion, which is reminiscent of a sporadic fusion in tumor cells, has the potential to cause chromosome instabilities. 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. The fused chromosome subsequently developed extra-acentric chromosomes, including chromosome scattering, indicative of chromothripsis. Live-cell imaging and statistical modeling indicated that sister chromatid fusion generated micronuclei (MN) in the first few cell cycles and that cells with MN tend to display cell cycle abnormalities. The powerful FuVis system thus demonstrates that even a single sporadic sister chromatid fusion can induce chromosome instability and destabilize the cell cycle through MN formation.