Chromosome mis-segregation during meiosis in oocytes causes miscarriages and congenital diseases. Aging-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 aging-associated meiotic errors in oocytes.
Yuanzhuo Zhou, Kohei Asai, Hirohisa Kyogoku, Tomoya S Kitajima (2025) Designing protein-based artificial kinetochores as decoys to prevent meiotic errors in oocytes., Nature cell biology
Published in 2025 Nov 4 (Electronic publication in Nov. 4, 2025, midnight )
(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.