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 A replicative helicase prevents asymmetric segregation of parental histones during DNA replication in mouse cells. During genome replication, parental histones are recycled to newly replicated DNA with their posttranslational modifications (PTMs). Whether sister chromatids inherit modified histones evenly remains unknown. We measured histone PTM partition to sister chromatids in embryonic stem cells. We found that parental histones H3-H4 segregate to both daughter DNA strands with a weak leading-strand bias, skewing partition at topologically associating domain (TAD) borders and enhancers proximal to replication initiation zones. Segregation of parental histones to the leading strand increased markedly in cells with histone-binding mutations in MCM2, part of the replicative helicase, exacerbating histone PTM sister chromatid asymmetry. This work reveals how histones are inherited to sister chromatids and identifies a mechanism by which the replication machinery ensures symmetric cell division.

中文翻译：

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MCM2促进DNA复制过程中修饰组蛋白的对称遗传

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 复制解旋酶可防止小鼠细胞 DNA 复制过程中亲本组蛋白的不对称分离。在基因组复制过程中，亲本组蛋白通过翻译后修饰 (PTM) 被回收到新复制的 DNA。姐妹染色单体是否均匀地继承了修饰的组蛋白仍然未知。我们测量了胚胎干细胞中组蛋白 PTM 对姐妹染色单体的分配。我们发现亲本组蛋白 H3-H4 与两条子 DNA 链分离，具有弱的前导链偏差，在拓扑关联域 (TAD) 边界和靠近复制起始区的增强子偏斜分区。在 MCM2（复制解旋酶的一部分）中具有组蛋白结合突变的细胞中，亲本组蛋白与前导链的分离显着增加，加剧了组蛋白 PTM 姐妹染色单体的不对称性。