RNA polymerase II associates with active genes during DNA replication

• Published in: Nature (London) 2023-08, Vol.620 (7973), p.426-433
• Main Authors: Fenstermaker, Tyler K., Petruk, Svetlana, Kovermann, Sina K., Brock, Hugh W., Mazo, Alexander
• Format: Article
• Language: English
• Subjects: 14/34; 14/63; 38/15; 631/208/176; 631/80/641/151/1431; 82/1; 82/29; Cell cycle; Chromatin; Deoxyribonucleic acid; DNA; DNA biosynthesis; DNA-directed RNA polymerase; Epigenetics; Genes; Humanities and Social Sciences; Labeling; multidisciplinary; Proteins; Replication; Ribonucleic acid; RNA; RNA polymerase; RNA polymerase II; Science; Science (multidisciplinary); Strands; Transcription
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/s41586-023-06341-9

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 1 , 2 . 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 3 , 4 . 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. Protein complexes containing RNA polymerase II and immature RNA are associated with active genes immediately after replication, suggesting that transmission of active transcriptional states to daughter cells may not require any additional epigenetic bookmarks.