How cells ensure symmetric inheritance Parental histones with modifications are recycled to newly replicated DNA strands during genome replication, but do the two sister chromatids inherit modified histones equally? Yu et al. and Petryk et al. found in mouse and yeast, respectively, that modified histones are segregated to both DNA daughter strands in a largely symmetric manner (see the Perspective by Ahmad and Henikoff). However, the mechanisms ensuring this symmetric inheritance in yeast and mouse were different. Yeasts use subunits of DNA polymerase to prevent the lagging-strand bias of parental histones, whereas in mouse cells, the replicative helicase MCM2 counters the leading-strand bias. Science, this issue p. 1386, p. 1389; see also p. 1311 DNA polymerase subunits prevent asymmetric segregation of parental histones during DNA replication in yeast. How parental histone (H3-H4)2 tetramers, the primary carriers of epigenetic modifications, are transferred onto leading and lagging strands of DNA replication forks for epigenetic inheritance remains elusive. Here we show that parental (H3-H4)2 tetramers are assembled into nucleosomes onto both leading and lagging strands, with a slight preference for lagging strands. The lagging-strand preference increases markedly in budding yeast cells lacking Dpb3 and Dpb4, two subunits of the leading strand DNA polymerase, Pol ε, owing to the impairment of parental (H3-H4)2 transfer to leading strands. Dpb3-Dpb4 binds H3-H4 in vitro and participates in the inheritance of heterochromatin. These results indicate that different proteins facilitate the transfer of parental (H3-H4)2 onto leading versus lagging strands and that Dbp3-Dpb4 plays an important role in this poorly understood process.

中文翻译：

---

一种防止不对称组蛋白分离到复制 DNA 链上的机制

细胞如何确保对称遗传在基因组复制过程中，经过修饰的亲本组蛋白被回收到新复制的 DNA 链中，但是两个姐妹染色单体是否同样继承了修饰的组蛋白？余等人。和佩特里克等人。分别在小鼠和酵母中发现，修饰的组蛋白以很大程度上对称的方式分离到两条 DNA 子链上（参见 Ahmad 和 Henikoff 的观点）。然而，在酵母和小鼠中确保这种对称遗传的机制是不同的。酵母使用 DNA 聚合酶的亚基来防止亲本组蛋白的滞后链偏向性，而在小鼠细胞中，复制解旋酶 MCM2 抵消前导链偏向性。科学，这个问题 p。1386 页。1389; 另见第。1311 DNA 聚合酶亚基可防止酵母 DNA 复制过程中亲本组蛋白的不对称分离。表观遗传修饰的主要载体亲本组蛋白 (H3-H4)2 四聚体如何转移到 DNA 复制叉的前导链和滞后链上以进行表观遗传仍然难以捉摸。在这里，我们展示了亲本 (H3-H4)2 四聚体组装到前导链和滞后链上的核小体中，对滞后链略有偏好。由于亲本 (H3-H4)2 向前导链的转移受损，在缺乏 Dpb3 和 Dpb4（前导链 DNA 聚合酶的两个亚基）的出芽酵母细胞中，滞后链偏好显着增加。Dpb3-Dpb4 在体外结合 H3-H4 并参与异染色质的遗传。