Slx5/Slx8 SUMO-targeted ubiquitin ligase deficiency shortens lifespan due to increased mutation accumulation in yeast

Chronological lifespan (CLS) in budding yeast Saccharomyces cerevisiae, which is defined as the time nondividing cells in saturation remain viable, has been utilized as a model to study post-mitotic aging in mammalian cells. CLS is closely related to entry into and maintenance of a quiescent state. Many rearrangements that direct the quiescent state enhance the ability of cells to endure several types of stress. Small ubiquitin-like modifier (SUMO)-targeted ubiquitin ligases (STUbLs) play a critical role in mediating an adaptive response to various stresses. In this study, we investigated the effect of a STUbL, Slx5/Slx8, on CLS in budding yeast. We showed that both SLX5 and SLX8 deletions accelerate chronological aging, resulting in a decreased maximum and mean lifespan. slx5 Delta cells were capable of entering or maintaining a quiescent state during aging. On the other hand, aging slx5 Delta and slx8 Delta cells had both increased spontaneous mutation accumulation. Our data together indicate that Slx5/Slx8 STUbL is required for normal rate of aging by preventing increased spontaneous mutation accumulation during aging. Slx5/Slx8 STUbL deficiency accelerates aging in yeast.