A mechanism for asymmetric segregation of age during yeast budding

Shcheprova, Zhanna; Baldi, Sandro; Frei, Stéphanie Buvelot; Gonnet, Gastón H.; Barral, Yves

doi:10.1038/nature07212

Cited by 304 publications

(412 citation statements)

References 46 publications

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“…They are inherited by the yeast mother cell, reducing her division potential with each subsequent division, compared with newborn daughter cells (3,32). The yeast mother cell also inherits the young spindle pole, the functional homolog of the young centrosome in mammalian cells (33).…”

Section: Discussionmentioning

confidence: 99%

Asymmetric partitioning of transfected DNA during mammalian cell division

Wang

Denoth-Lippuner

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Foreign DNA molecules and chromosomal fragments are generally eliminated from proliferating cells, but we know little about how mammalian cells prevent their propagation. Here, we show that dividing human and canine cells partition transfected plasmid DNA asymmetrically, preferentially into the daughter cell harboring the young centrosome. Independently of how they entered the cell, most plasmids clustered in the cytoplasm. Unlike polystyrene beads of similar size, these clusters remained relatively immobile and physically associated to endoplasmic reticulum-derived membranes, as revealed by live cell and electron microscopy imaging. At entry of mitosis, most clusters localized near the centrosomes. As the two centrosomes split to assemble the bipolar spindle, predominantly the old centrosome migrated away, biasing the partition of the plasmid cluster toward the young centrosome. Down-regulation of the centrosomal proteins Ninein and adenomatous polyposis coli abolished this bias. Thus, we suggest that DNA clustering, cluster immobilization through association to the endoplasmic reticulum membrane, initial proximity between the cluster and centrosomes, and subsequent differential behavior of the two centrosomes together bias the partition of plasmid DNA during mitosis. This process leads to their progressive elimination from the proliferating population and might apply to any kind of foreign DNA molecule in mammalian cells. Furthermore, the functional difference of the centrosomes might also promote the asymmetric partitioning of other cellular components in other mammalian and possibly stem cells.foreign DNA | asymmetric cell division | centrosome | endoplasmic reticulum | Ninein G enerally, noncentromeric DNA molecules are mitotically instable in eukaryotes. This results in their apparent disappearance from an ever-increasing proportion of the progeny of an affected cell (e.g., 1-3). Endogenous sources of such DNA are recombination byproducts [double minutes, extrachromosomal ribosomal (r)DNA circles (ERCs) and other DNA circles (3-6)] or mitotic defects generating noncentromeric chromosomal fragments and cytoplasmic micronuclei (1, 7). Exogenous sources are DNA of pathogens or DNA, typically plasmids, artificially introduced into cells. For the latter, decades of work established that plasmid-born protein expression is transient, persisting only for a few cell cycles (8). This finding is consistent with plasmid DNA being somehow eliminated through divisions. Thus, some mechanisms seem to prevent the propagation of foreign DNA and extrachromosomal DNA in proliferating eukaryotic cells. However, how this is achieved is unclear.In animal cells, DNA sensors mediate the early detection of exogenous DNA, such as DNA of invading pathogens and artificially introduced DNA (9-11). Both in leukocytes and nonprofessional immune cells, these can trigger innate immune responses, such as cytokine production, autophagy, and apoptosis (9). However, what happens to the DNA molecules themselves over time is unclear. When microi...

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Section: Discussionmentioning

confidence: 99%

Asymmetric partitioning of transfected DNA during mammalian cell division

Wang

Denoth-Lippuner

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…In particular, the segregation of NPCs is controversial, with two opposing models currently dominating the field. On the basis of photobleaching experiments it has been suggested that preexisting NPCs are retained by the mother cell, whereas only new NPCs are incorporated into the bud (24). By contrast, experiments with nucleoporins tagged with a photoconvertible fluorescent protein suggested that maternal NPCs migrate into the daughter cell (25).…”

Section: Old and New Proteins Are Homogeneously Distributed In Mostmentioning

confidence: 99%

Spatiotemporal analysis of organelle and macromolecular complex inheritance

Menéndez‐Benito¹,

Deventer²,

Jimenez-Garcia³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Following mitosis, daughter cells must inherit a functional set of essential proteins and organelles. We applied a genetic tool to simultaneously monitor the kinetics and distribution of old and new proteins marking all intracellular compartments in budding yeasts. Most organelles followed a general pattern whereby preexisting proteins are symmetrically partitioned followed by template-based incorporation of new proteins. Peroxisomes belong to this group, supporting a model of biogenesis by growth and division from preexisting peroxisomes. We detected two exceptions: the nuclear pore complex (NPC) and the spindle pole body (SPB). Old NPCs are stably inherited during successive generations but remained separated from new NPCs, which are incorporated de novo in mother and daughter cells. Only the SPB displayed asymmetrical distribution, with old components primarily inherited by daughter cells and new proteins equally incorporated in both cells. Our analysis resolves conflicting models (peroxisomes, NPC) and reveals unique patterns (NPC, SPB) of organelle inheritance.Saccharomyces cerevisiae | protein dynamics | nuclear envelope | centrosome | live-cell imaging

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“…The newly born daughter cell or the bud is approximately two-thirds of its mother in size. A transcriptional repressor, Ash1, is localized exclusively in the daughter cell to silence its ability in mating-type switching [Bobola et al, 1996;Jansen et al, 1996], whereas aging factors are restricted to the mother cell [Shcheprova et al, 2008;Khmelinskii et al, 2011;Zhou et al, 2011]. Immediately following cytokinesis (complete membrane closure between two forming cells), a transcriptional program called the RAM pathway (Regulation of Ace2 activity and Cellular Morphogenesis) is activated exclusively in the daughter cell to ensure proper cell separation [Bidlingmaier et al, 2001;Colman-Lerner et al, 2001;Nelson et al, 2003] (see more discussion later).…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of cytokinesis in budding yeast

Wloka

2012

Cytoskeleton

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Cytokinesis is essential for cell proliferation in all domains of life. Because the core components and mechanisms of cytokinesis are conserved from fungi to humans, the budding yeast Saccharomyces cerevisiae has served as an attractive model for studying this fundamental process. Cytokinesis in budding yeast is driven by two interdependent cellular events: actomyosin ring (AMR) constriction and the formation of a chitinous cell wall structure called the primary septum (PS), the functional equivalent of extracellular matrix remodeling during animal cytokinesis. AMR constriction is thought to drive efficient plasma membrane ingression as well as to guide PS formation, whereas PS formation is thought to stabilize the AMR during its constriction. Following the completion of the PS formation, two secondary septa (SS), consisting of glucans and mannoproteins, are synthesized at both sides of the PS. Degradation of the PS and a part of the SS by a chitinase and glucanases then enables cell separation. In this review, we discuss the mechanics of cytokinesis in budding yeast, highlighting its common and unique features as well as the emerging questions. © 2012 Wiley Periodicals, Inc.

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A mechanism for asymmetric segregation of age during yeast budding

Cited by 304 publications

References 46 publications

Asymmetric partitioning of transfected DNA during mammalian cell division

Asymmetric partitioning of transfected DNA during mammalian cell division

Spatiotemporal analysis of organelle and macromolecular complex inheritance

Mechanisms of cytokinesis in budding yeast

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