The dynamic nuclear periphery as a facilitator of gamete health and rejuvenation

The nuclear periphery is a hotspot for the accumulation of age-induced damage in eukaryotic cells. The types of damage that occur at the periphery and their phenotypic consequences have begun to be characterized; however, the mechanisms by which cells repair or eliminate nuclear damage remain poorly understood. Using budding yeast meiosis as a natural system to study cellular rejuvenation, we recently discovered a novel nuclear quality control event, in which age-induced damage is sequestered away from dividing chromosomes to a discarded nuclear compartment that we term the GUNC (for "Gametogenesis Uninherited Nuclear Compartment"). Interestingly, extensive nuclear remodeling occurs even in young cells, including a surprising modularity of the nuclear pore complex, suggesting a general contribution to gamete fitness. In this review, we discuss these findings in the context of recent evidence that the nuclear periphery is a highly dynamic region critical for cellular health.