Designing protein-based artificial kinetochores as decoys to prevent meiotic errors in oocytes

设计基于蛋白质的人工着丝粒作为诱饵,以防止卵母细胞减数分裂错误

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Abstract

Chromosome mis-segregation during meiosis in oocytes causes miscarriages and congenital diseases. Ageing-associated premature chromosome separation is a major cause of mis-segregation. Effective prevention of premature chromosome separation has not yet been achieved. Here we design protein-based artificial kinetochores that act as decoys to prevent premature chromosome separation. Designed artificial kinetochore-like decoys are submicroscale clusters of NDC80-NUF2-tethered protein particles that can establish a biorientation-like state by competing with chromosomal kinetochores for HURP-decorated microtubules. This competition reduces excessive bipolar microtubule pulling forces exerted on chromosomes, thereby effectively preventing premature chromosome separation during meiosis I and II in aged mouse oocytes. These effects suppress egg aneuploidy. This study provides a decoy strategy with biocompatible artificial kinetochores to prevent ageing-associated meiotic errors in oocytes.

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