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Slx5/Slx8 SUMO-targeted ubiquitin ligase deficiency shortens lifespan due to increased mutation accumulation in yeast
(Oxford Univ Press, 2025) Thomas, Pinar B.; Kaluc, Nur; Cavli, Irmak N.; Tuna, Bilge G.
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.