RT Journal Article SR Electronic T1 Chromosome instability induced by a single defined sister chromatid fusion JF Life Science Alliance JO Life Sci. Alliance FD Life Science Alliance LLC SP e202000911 DO 10.26508/lsa.202000911 VO 3 IS 12 A1 Kagaya, Katsushi A1 Noma-Takayasu, Naoto A1 Yamamoto, Io A1 Tashiro, Sanki A1 Ishikawa, Fuyuki A1 Hayashi, Makoto T YR 2020 UL http://www.life-science-alliance.org/content/3/12/e202000911.abstract 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.