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The ultimate success of cell division relies on the accurate partitioning of the genetic material. Errors in this process occur in nearly all tumors and are the leading cause of miscarriages and congenital birth defects in humans. Two cell divisions, mitosis and meiosis, use common as well as unique mechanisms to ensure faithful chromosome segregation. In mitosis, alternating rounds of DNA replication and chromosome segregation preserve the chromosome complement of the progenitor cell. In contrast, during meiosis two consecutive rounds of nuclear division, meiosis I and meiosis II, follow a single round of DNA replication to reduce the chromosome complement by half. Meiosis likely evolved through changes to the mitotic cell division program. This review will focus on the recent findings describing the modifications that transform mitosis into meiosis.

Gametogenesis is a process whereby a germ cell differentiates into haploid gametes. We found that, in budding yeast, replicatively aged cells remove age-induced cellular damage during gametogenesis. Importantly, gametes of aged cells have the same replicative potential as those derived from young cells, indicating that life span resets during gametogenesis. Here, we explore the potential mechanisms responsible for gametogenesis-induced rejuvenation and discuss putative analogous mechanisms in higher eukaryotes., National Institutes of Health (U.S.) (grant GM62207)

Eukaryotic organisms age, yet detrimental age-associated traits are not passed on to progeny. How life span is reset from one generation to the next is not known. We show that in budding yeast resetting of life span occurs during gametogenesis. Gametes (spores) generated by aged cells show the same replicative potential as gametes generated by young cells. Age-associated damage is no longer detectable in mature gametes. Furthermore, transient induction of a transcription factor essential for later stages of gametogenesis extends the replicative life span of aged cells. Our results indicate that gamete formation brings about rejuvenation by eliminating age-induced cellular damage., National Institutes of Health (U.S.) (Grant GM62207)

During meiosis, a single round of DNA replication is followed by two consecutive rounds of nuclear divisions called meiosis I and meiosis II. In meiosis I, homologous chromosomes segregate, while sister chromatids remain together. Determining how this unusual chromosome segregation behavior is established is central to understanding germ cell development. Here we show that preventing microtubule–kinetochore interactions during premeiotic S phase and prophase I is essential for establishing the meiosis I chromosome segregation pattern. Premature interactions of kinetochores with microtubules transform meiosis I into a mitosis-like division by disrupting two key meiosis I events: coorientation of sister kinetochores and protection of centromeric cohesin removal from chromosomes. Furthermore we find that restricting outer kinetochore assembly contributes to preventing premature engagement of microtubules with kinetochores. We propose that inhibition of microtubule–kinetochore interactions during premeiotic S phase and prophase I is central to establishing the unique meiosis I chromosome segregation pattern., Howard Hughes Medical Institute, National Institutes of Health (U.S.) (grant GM62207), Jane Coffin Childs Memorial Fund for Medical Research, American Cancer Society

In humans, the frequency with which meiotic chromosome mis-segregation occurs increases with age. Whether age-dependent meiotic defects occur in other organisms is unknown. Here, we examine the effects of replicative aging on meiosis in budding yeast. We find that aged mother cells show a decreased ability to initiate the meiotic program and fail to express the meiotic inducer IME1. The few aged mother cells that do enter meiosis complete this developmental program but exhibit defects in meiotic chromosome segregation and spore formation. Furthermore, we find that mutations that extend replicative life span also extend the sexual reproductive life span. Our results indicate that in budding yeast, the ability to initiate and complete the meiotic program as well as the fidelity of meiotic chromosome segregation decrease with cellular age and are controlled by the same pathways that govern aging of asexually reproducing yeast cells., National Institutes of Health (U.S.) (Grant number GM62207), National Science Foundation (U.S.). (Grant number MCB-0342285), Howard Hughes Medical Institute. Investigator

In humans, the frequency with which meiotic chromosome mis-segregation occurs increases with age. Whether age-dependent meiotic defects occur in other organisms is unknown. Here, we examine the effects of replicative aging on meiosis in budding yeast. We find that aged mother cells show a decreased ability to initiate the meiotic program and fail to express the meiotic inducer IME1. The few aged mother cells that do enter meiosis complete this developmental program but exhibit defects in meiotic chromosome segregation and spore formation. Furthermore, we find that mutations that extend replicative life span also extend the sexual reproductive life span. Our results indicate that in budding yeast, the ability to initiate and complete the meiotic program as well as the fidelity of meiotic chromosome segregation decrease with cellular age and are controlled by the same pathways that govern aging of asexually reproducing yeast cells., National Institutes of Health (U.S.) (Grant number GM62207), National Science Foundation (U.S.). (Grant number MCB-0342285), Howard Hughes Medical Institute. Investigator