Science Advances

Prefoldin function links meiotic chromosome segregation with cellular remodeling and reveals tubulin sensitivity of the meiotic spindle

2026-08-26

Faithful chromosome segregation is essential for producing viable gametes during meiosis, a specialized type of cell division relative to mitosis. Here we identify Gim3, a subunit of the ubiquitously expressed and conserved prefoldin complex, as a critical regulator of meiotic but not mitotic chromosome segregation in budding yeast. Loss of Gim3 causes profound defects in chromosome segregation and gamete viability through reduced tubulin protein levels, which are also associated with reduced spindle length. In mitosis, GIM3 deletion minimally affects spindle length and chromosome segregation, despite similarly reduced tubulin levels in both contexts, highlighting an intriguing difference between the sensitivity of meiotic and mitotic spindles to tubulin abundance. Beyond chromosome segregation defects, gim3 ∆ cells exhibit aberrant meiotic cellular remodeling, including defects in exclusion of age-associated protein aggregates from newly forming gametes. Independently induced meiotic chromosome missegregation similarly disturbs cellular remodeling, pointing to a fundamental coupling between these aspects of gamete production. Together, our findings identify Gim3 as a key factor required for maintaining meiotic chromosome segregation integrity, and reveal an exciting and previously unrecognized link between chromosome segregation and meiotic cellular remodeling.

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DOI https://doi.org/10.1126/sciadv.aef5385