Proteomic profiling reveals distinct phases to the restoration of chromatin following DNA replication
Proteomic profiling reveals distinct phases to the restoration of chromatin following DNA replication
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DOI：
10.1016/j.celrep.2023.111996
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发表时间：
2023-01-20
期刊：
影响因子：
8.8
通讯作者：
Alabert, Constance
中科院分区：
文献类型：
--
作者：
Alvarez, Vanesa;Bandau, Susanne;Alabert, Constance
细胞增殖期间必须维持染色质组织，以保持细胞身份和基因组完整性。然而，DNA复制会导致DNA结合蛋白的瞬时位移，目前还不清楚它们如何重新获得新复制的DNA。使用定量蛋白质组学结合新生染色质捕获或新生DNA上蛋白质的分离，我们提供了人类细胞中常染色质和异染色质内复制体后面数千种蛋白质的时间分辨结合动力学。这表明大多数蛋白质在几分钟内重新获得新复制的DNA。相比之下，25%的蛋白质没有，这种延迟不能从它们已知的功能或核丰度推断出来。相反，染色质组织和G1期进入影响它们的重新结合。最后，DNA复制不仅中断，而且促进转录因子和染色质重塑的招募，为理解DNA复制如何有助于细胞记忆的程序性变化提供了重大进展。
Chromatin organization must be maintained during cell proliferation to preserve cellular identity and genome integrity. However, DNA replication results in transient displacement of DNA-bound proteins, and it is unclear how they regain access to newly replicated DNA. Using quantitative proteomics coupled to Nascent Chromatin Capture or isolation of Proteins on Nascent DNA, we provide time-resolved binding kinetics for thousands of proteins behind replisomes within euchromatin and heterochromatin in human cells. This shows that most proteins regain access within minutes to newly replicated DNA. In contrast, 25% of the identified proteins do not, and this delay cannot be inferred from their known function or nuclear abundance. Instead, chromatin organization and G1 phase entry affect their reassociation. Finally, DNA replication not only dis-rupts but also promotes recruitment of transcription factors and chromatin remodelers, providing a significant advance in understanding how DNA replication could contribute to programmed changes of cell memory.