Artificial kinetochore beads establish a biorientation-like state in the spindle

• 成果类型: Article
• 署名作者: Asai, Kohei; Zhou, Yuanzhuo; Takenouchi, Osamu; Kitajima, Tomoya S.
• 署名单位: RIKEN; Kyoto University
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8136
• DOI: 10.1126/science.adn5428
• 发表日期: 2024-09-20
• 关键词: chromosome bi-orientation; microtubule attachment; self-organization; ska complex; cenp-a; protein; binding; segregation; kinase; architecture

摘要

Faithful chromosome segregation requires biorientation, where the pair of kinetochores on the chromosome establish bipolar microtubule attachment. The integrity of the kinetochore, a macromolecular complex built on centromeric DNA, is required for biorientation, but components sufficient for biorientation remain unknown. Here, we show that tethering the outer kinetochore heterodimer NDC80-NUF2 to the surface of apolar microbeads establishes their biorientation-like state in mouse cells. NDC80-NUF2 microbeads align at the spindle equator and self-correct alignment errors. The alignment is associated with stable bipolar microtubule attachment and is independent of the outer kinetochore proteins SPC24-SPC25, KNL1, the Mis12 complex, inner kinetochore proteins, and Aurora. Larger microbeads align more rapidly, suggesting a size-dependent biorientation mechanism. This study demonstrates a biohybrid kinetochore design for synthetic biorientation of microscale particles in cells.