Role of SAGA in the asymmetric segregation of DNA circles during yeast ageing.
Role of SAGA in the asymmetric segregation of DNA circles during yeast ageing.
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DOI：
10.7554/elife.03790
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发表时间：
2014-11-17
期刊：
影响因子：
7.7
通讯作者：
Barral Y
中科院分区：
文献类型：
--
作者：
Denoth-Lippuner A;Krzyzanowski MK;Stober C;Barral Y
在真核生物中，染色体内重组会产生DNA回路，但对细胞在酵母中的反应几乎不知所措在这项研究中进行了辩论。促进其在母细胞中的限制。母细胞，从而促进衰老，我们的数据为DNA电路的不对称隔离提供了统一的模型，以及年龄如何影响核组织。
doi：http：//dx.doi.org/10.7554/elife.03790.001
出现的酵母是一种微生物，它已经广泛研究了它和许多其他生物，包括动物，随着时间的流逝，它是因为它通过“萌芽”的子细胞而来的每个芽的女儿细胞，母细胞失去了一些健身，最终在一定数量的萌芽事件中死亡。相比之下，干细胞的年龄实质上是“重置为零”，直到他们变成母细胞本身。
几个分子或因素与复制衰老有关。随着时间的流逝，这会积聚在老化的母细胞内。
与动植物类似，酵母细胞中的染色体被限制在称为细胞核us的膜结构中。现在，DeNoth-Lippener等人确定非染色体DNA电路有效地限制在母细胞中复合物。
DENOTH-LIPPENER等人如何将DNA回路锚定在这些复合物上，并发现在萌芽的酵母菌中删除了一种称为SAGA的蛋白质。另一方面，也将这些DNA电路锚定在核孔复合体上，以减轻了对传奇综合体的需求，以保留这些分子在母细胞中。
Demoth-Lippener等人还表明，DNA回路依赖于核孔复合物，导致这些复合物留在母细胞中然而，子细胞中的核孔复合物仍然相当恒定。因为它们对衰老的贡献，也许是通过影响细胞核的工作。
doi：http：//dx.doi.org/10.7554/elife.03790.002
In eukaryotes, intra-chromosomal recombination generates DNA circles, but little is known about how cells react to them. In yeast, partitioning of such circles to the mother cell at mitosis ensures their loss from the population but promotes replicative ageing. Nevertheless, the mechanisms of partitioning are debated. In this study, we show that the SAGA complex mediates the interaction of non-chromosomal DNA circles with nuclear pore complexes (NPCs) and thereby promotes their confinement in the mother cell. Reciprocally, this causes retention and accumulation of NPCs, which affects the organization of ageing nuclei. Thus, SAGA prevents the spreading of DNA circles by linking them to NPCs, but unavoidably causes accumulation of circles and NPCs in the mother cell, and thereby promotes ageing. Together, our data provide a unifying model for the asymmetric segregation of DNA circles and how age affects nuclear organization. DOI: http://dx.doi.org/10.7554/eLife.03790.001 Budding yeast is a microorganism that has been widely studied to understand how it and many other organisms, including animals, age over time. This yeast is so named because it proliferates by ‘budding’ daughter cells out of the surface of a mother cell. For each daughter cell that buds, the mother cell loses some fitness and eventually dies after a certain number of budding events. This process is called ‘replicative ageing’, and it also resembles the way that stem cells age. In contrast, the newly formed daughters essentially have their age ‘reset to zero’ and grow until they turn into mother cells themselves. Several molecules or factors have been linked to replicative ageing. These are retained in the mother cell during budding, rather than being passed on to the daughters. Non-chromosomal DNA circles, for example, are rings of DNA that detach from chromosomes during DNA repair and that accumulate inside the ageing mother cell over time. How the mother cells retain these circles of DNA is an on-going topic of debate. Similar to plants and animals, chromosomes in yeast cells are confined in a membrane-bound structure known as the cell nucleus. The nuclear membrane is perforated by channels called nuclear pore complexes that ensure the transport of molecules into, and out of, the nucleus. Now, Denoth-Lippuner et al. establish that for the non-chromosomal DNA circles to be efficiently confined in the mother cell, the DNA circles must be anchored to the nuclear pore complexes. Denoth-Lippuner et al. next asked how the DNA circles were anchored to these complexes; and found that another complex of proteins known as SAGA is involved. When components of the SAGA complex were deleted in budding yeast cells, non-chromosomal DNA circles spread into the daughters as well. On the other hand, artificially anchoring these DNA circles to the nuclear pore complex alleviated the need for the SAGA complex, in order to retain these molecules in the mother cell. Denoth-Lippuner et al. also show that SAGA-dependent attachment of the DNA circles to the nuclear pore complexes causes these complexes to remain in the mother cell. As a consequence, these nuclear pore complexes accumulate in the mother cells as they age. The number of nuclear pore complexes in the daughter cells, however, remained fairly constant. Together these data raise the question of whether the effects of DNA circles on the number and activity of the nuclear pores might account for their contribution to ageing, perhaps by affecting the workings of the nucleus. DOI: http://dx.doi.org/10.7554/eLife.03790.002