Mihailo Mirkovic

eLife Assessment This fundamental study reveals that aging in yeast leads to chromosome mis-segregation due to asymmetric partitioning of chromosomes, driven by disruption of the nuclear pore complex and pre-mRNA leakage. The findings are convincingly supported by carefully-designed experimental data with a combination of genetic, molecular biology and cell biology approaches.

Abstract In many organisms, aging is a clear risk factor for increased rates of chromosome mis-segregation, the main source of aneuploidy. Here, we report that old yeast mother cells lose chromosomes by partitioning them asymmetrically to their daughter cells together with the pre-existing (old) SPB (centrosome equivalent in yeast). Strikingly, remodeling of the NPC and the displacement of its nuclear basket triggered these asymmetric segregation events.

(A) Images from movies of the wing disc pouch in the control, san RNAi, and san and mad2 RNAi strains. Strains contained HisH2Av-RFP (red) and Cid-EGFP (green). Times are relative to NEBD. The scale bar represents 5 μm. (B) Quantification of mitotic duration in control, san RNAi, or san and mad2 RNAi strains. The duration of mitosis was measured from nuclear envelope breakdown (NEBD) to nuclear envelope formation (NEF) using H2Av-RFP channel. Images were taken every 2 min.