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- W4364353313 abstract "Various cancer types exhibit characteristic and recurrent aneuploidy patterns. The origins of these cancer type-specific karyotypes are still unknown, partly because introducing or eliminating specific chromosomes in human cells still poses a challenge. Here, we describe a novel strategy to induce mis-segregation of specific chromosomes in different human cell types. We employed Tet repressor or nuclease-dead Cas9 to link a microtubule minus-end-directed kinesin (Kinesin14VIb) from Physcomitrella patens to integrated Tet operon repeats and chromosome-specific endogenous repeats, respectively. By live- and fixed-cell imaging, we observed poleward movement of the targeted loci during (pro)metaphase. Kinesin14VIb-mediated pulling forces on the targeted chromosome were counteracted by forces from kinetochore-attached microtubules. This tug-of-war resulted in chromosome-specific segregation errors during anaphase and revealed that spindle forces can heavily stretch chromosomal arms. By single-cell whole-genome sequencing, we established that kinesin-induced targeted mis-segregations predominantly result in chromosomal arm aneuploidies after a single cell division. Our kinesin-based strategy opens the possibility to investigate the immediate cellular responses to specific aneuploidies in different cell types; an important step toward understanding how tissue-specific aneuploidy patterns evolve." @default.
- W4364353313 created "2023-04-12" @default.
- W4364353313 creator A5002472661 @default.
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- W4364353313 creator A5090303159 @default.
- W4364353313 date "2023-04-11" @default.
- W4364353313 modified "2023-10-15" @default.
- W4364353313 title "A kinesin‐based approach for inducing chromosome‐specific mis‐segregation in human cells" @default.
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- W4364353313 doi "https://doi.org/10.15252/embj.2022111559" @default.
- W4364353313 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37038978" @default.
- W4364353313 hasPublicationYear "2023" @default.
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