Replication Stress Interferes with Histone Recycling and Predeposition Marking of New Histones
Replication Stress Interferes with Histone Recycling and Predeposition Marking of New Histones
复制标题
DOI：
10.1016/j.molcel.2010.01.033
复制
发表时间：
2010-03-12
期刊：
影响因子：
16
通讯作者：
Groth, Anja
中科院分区：
文献类型：
--
作者：
Jasencakova, Zuzana;Scharf, Annette N. D.;Groth, Anja
为了在复制过程中恢复新 DNA 上的染色质，在分叉之前驱逐的组蛋白的回收与新组蛋白的沉积相结合。 Asf1 组蛋白伴侣可以在压力下缓冲多余的组蛋白，是这一过程中的关键角色。然而，人类 Asf1 处理的组蛋白是如何被修饰的仍不清楚。在这里，我们鉴定了与 Asf1 结合的组蛋白 H3-H4 上的标记以及复制应激引起的变化。在 S 期，不同的胞质和核 Asf1b 复合物显示出普遍存在的 H4K5K12diAc 和异质 H3 标记，包括 K9me1、K14ac、K18ac 和 K56ac。急性复制停滞后，预沉积标记 H3K9me1 和染色质典型修饰在 Asf1 复合物中积累。与此同时，ssDNA 在复制位点生成，与 Asf1 捕获的被逐出的组蛋白一致。在恢复过程中，随着复制的恢复，与 Asf1 一起存储的组蛋白会被快速使用。这表明复制应激会干扰预沉积标记和组蛋白回收，并对表观遗传稳定性产生潜在影响。
To restore chromatin on new DNA during replication, recycling of histones evicted ahead of the fork is combined with new histone deposition. The Asf1 histone chaperone, which buffers excess histones under stress, is a key player in this process. Yet how histones handled by human Asf1 are modified remains unclear. Here we identify marks on histones H3-H4 bound to Asf1 and changes induced upon replication stress. In S phase, distinct cytosolic and nuclear Asf1b complexes show ubiquitous H4K5K12diAc and heterogeneous H3 marks, including K9me1, K14ac, K18ac, and K56ac. Upon acute replication arrest, the predeposition mark H3K9me1 and modifications typical of chromatin accumulate in Asf1 complexes. In parallel, ssDNA is generated at replication sites, consistent with evicted histones being trapped with Asf1. During recovery, histones stored with Asf1 are rapidly used as replication resumes. This shows that replication stress interferes with predeposition marking and histone recycling with potential impact on epigenetic stability.