Persistence of RNA transcription during DNA replication delays duplication of transcription start sites until G2/M.
Persistence of RNA transcription during DNA replication delays duplication of transcription start sites until G2/M.
复制标题
在DNA复制过程中，RNA转录的持续性会将转录起始点的复制延迟到G2/M。
DOI：
10.1016/j.celrep.2021.108759
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发表时间：
2021-02-16
期刊：
影响因子：
8.8
通讯作者：
Saponaro M
中科院分区：
文献类型：
--
作者：
Wang J;Rojas P;Mao J;Mustè Sadurnì M;Garnier O;Xiao S;Higgs MR;Garcia P;Saponaro M
由于转录和复制使用DNA作为底物，转录和复制之间可能发生冲突，导致基因组不稳定，对人类健康产生直接影响。为了确定这两个过程是如何在整个S阶段协调，我们表征这两个过程一起在高分辨率。我们发现，转录发生在DNA复制，转录起始位点（TSS）不完全复制沿着与周围地区，并保持复制不足，直到在细胞周期的后期。当RNA聚合酶II被去除时，TSS特别是当细胞进入有丝分裂时完成DNA复制。有趣的是，G2/M DNA合成在未受干扰的细胞培养中以高频率发生，但它与DNA损伤增加无关，并且从根本上与有丝分裂DNA合成分离。在G2/M期复制的TSS具有一系列特异性特征，包括高水平的反义转录，使得它们难以在S期复制。在DNA复制过程中，RNA聚合酶II在转录起始位点保持活性。数百个基因的转录起始位点仅在G2/M期复制G2/M期DNA合成（G-MiDS）与DNA损伤修复过程无关G-MiDS与有丝分裂DNA合成（MiDAS）分离。显示了人类细胞中转录和复制是如何相互影响的。他们发现转录起始位点并没有与其邻近区域一起完全复制，并观察了数百个只有当细胞进入有丝分裂时才完成复制的案例。
As transcription and replication use DNA as substrate, conflicts between transcription and replication can occur, leading to genome instability with direct consequences for human health. To determine how the two processes are coordinated throughout S phase, we characterize both processes together at high resolution. We find that transcription occurs during DNA replication, with transcription start sites (TSSs) not fully replicated along with surrounding regions and remaining under-replicated until late in the cell cycle. TSSs undergo completion of DNA replication specifically when cells enter mitosis, when RNA polymerase II is removed. Intriguingly, G2/M DNA synthesis occurs at high frequency in unperturbed cell culture, but it is not associated with increased DNA damage and is fundamentally separated from mitotic DNA synthesis. TSSs duplicated in G2/M are characterized by a series of specific features, including high levels of antisense transcription, making them difficult to duplicate during S phase. During DNA replication, RNA polymerase II remains active at transcription start sites Transcription start sites of hundreds of genes are duplicated only in G2/M G2/M DNA synthesis (G-MiDS) is not associated with DNA damage repair processes G-MiDS is separated from mitotic DNA synthesis (MiDAS) Wang et al. show how transcription and replication affect each other in human cells. They find that transcription start sites are not fully replicated together with their neighboring regions and observe hundreds of cases in which duplication is completed only when cells are entering mitosis.
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