Department of Biochemistry and Molecular Biology, Sidney Kimmel Medical College, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
Department of Zoology, University of British Columbia, Vancouver, British Columbia, Canada.
Nature. 2023 Aug;620(7973):426-433. doi: 10.1038/s41586-023-06341-9. Epub 2023 Jul 19.
The transcriptional machinery is thought to dissociate from DNA during replication. Certain proteins, termed epigenetic marks, must be transferred from parent to daughter DNA strands in order to maintain the memory of transcriptional states. These proteins are believed to re-initiate rebuilding of chromatin structure, which ultimately recruits RNA polymerase II (Pol II) to the newly replicated daughter strands. It is believed that Pol II is recruited back to active genes only after chromatin is rebuilt. However, there is little experimental evidence addressing the central questions of when and how Pol II is recruited back to the daughter strands and resumes transcription. Here we show that immediately after passage of the replication fork, Pol II in complex with other general transcription proteins and immature RNA re-associates with active genes on both leading and lagging strands of nascent DNA, and rapidly resumes transcription. This suggests that the transcriptionally active Pol II complex is retained in close proximity to DNA, with a Pol II-PCNA interaction potentially underlying this retention. These findings indicate that the Pol II machinery may not require epigenetic marks to be recruited to the newly synthesized DNA during the transition from DNA replication to resumption of transcription.
转录机制被认为在复制过程中会从 DNA 上解离。某些被称为表观遗传标记的蛋白质,必须从亲代 DNA 链转移到子代 DNA 链,以维持转录状态的记忆。这些蛋白质被认为重新启动了染色质结构的重建,最终将 RNA 聚合酶 II(Pol II)招募到新复制的子链上。人们认为,只有在重建染色质后,Pol II 才会重新招募到活性基因上。然而,几乎没有实验证据能够解决 Pol II 何时以及如何重新招募到子链并恢复转录的核心问题。在这里,我们表明,在复制叉通过后立即,与其他一般转录蛋白和不成熟 RNA 结合的 Pol II 重新与新生 DNA 的前导链和滞后链上的活性基因结合,并迅速恢复转录。这表明转录活性的 Pol II 复合物与 DNA 紧密接近,Pol II-PCNA 相互作用可能是这种保留的基础。这些发现表明,在从 DNA 复制到恢复转录的过渡过程中,Pol II 机制可能不需要表观遗传标记来招募到新合成的 DNA 上。