The establishment of heterochromatin in fission yeast involves methyltransferase Clr4-mediated H3-Lys9 methylation, which is bound specifically by Swi6/HP1. The structure spreads further through cooperative action of Swi6 and Clr4. While the mechanism of establishment and spreading of heterochromatin is somewhat well understood, that of its propagation through multiple cell divisions is not so well known. One model has invoked the role of DNA replication in propagating the heterochromatin both in S. cerevisiae and S. pombe. Studies in S. pombe have indicated a direct interaction between DNA Polα and Swi6/HP1 and between DNA Polε and Rik1-Dos2 complex, suggesting that the processes of DNA replication and heterochromatin assembly may be tightly coupled. Here, we show that like DNA Polα, Polδ, which plays a role in both leading and lagging strand replication, also plays a role in silencing at mating type and centromere. Interestingly, we show that both the polymerases interact directly with both the heterochromatin code writer Clr4 and reader, Swi6/HP1. Mutations in both the polymerases lead to decrease in H3-Lys9 methylation and Swi6 at the mating-type and left outer repeats of centromeres I and II, with a reciprocal increase in their level at the central element, cnt, at all the three centromeres. Mutations in the catalytic subunits of polα and polδ also elicit defects in chromosome segregation, recruitment of Cohesin and chromosome dynamics both during mitosis and meiosis. Thus, our results indicate that direct interaction of the DNA replication machinery with the epigenetic machinery coordinates the propagation of the heterochromatin-specific epigenetic mark and proper cohesion recruitment and chromosome segregation during mitosis and meiosis.

中文翻译：

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异染色质复制：DNA复制机制与异染色质代码编写器Clr4 / Suv39和阅读器Swi6 / HP1在粟酒裂殖酵母中的直接相互作用

在裂变酵母中建立异染色质涉及甲基转移酶Clr4介导的H3-Lys9甲基化，该甲基化被Swi6 / HP1特异性结合。该结构通过Swi6和Clr4的协同作用进一步传播。虽然异染色质的建立和扩散机制已为人们所熟知，但其跨多个细胞分裂的传播机制还不是很清楚。一种模型在酿酒酵母和粟酒裂殖酵母中都发挥了DNA复制在异染色质繁殖中的作用。粟酒裂殖酵母的研究已经表明DNAPolα和Swi6 / HP1之间以及DNAPolε和Rik1-Dos2复合物之间存在直接相互作用，这表明DNA复制和异染色质组装过程可能紧密耦合。在这里，我们显示出与DNAPolα一样，Polδ在前导链和滞后链的复制中均起作用，在交配类型和着丝粒的沉默中也起作用。有趣的是，我们表明这两种聚合酶都直接与异染色质代码编写器Clr4和阅读器Swi6 / HP1相互作用。两种聚合酶的突变均导致着丝粒I和II的交配型和左外侧重复序列的H3-Lys9甲基化和Swi6减少，而在所有三个着丝粒的中央元件cnt的水平却相互升高。polα和polδ催化亚基的突变也会在有丝分裂和减数分裂过程中引起染色体分离，凝聚素募集和染色体动力学缺陷。因此，我们的结果表明，DNA复制机制与表观遗传机制的直接相互作用，协调了异染色质特异性表观遗传标记的传播以及有丝分裂和减数分裂过程中适当的内聚募集和染色体分离。