Transcription-replication coordination revealed in single live cells

Ioannis Tsirkas, Daniel Dovrat, Manikandan Thangaraj, Ineke Brouwer, Amit Cohen, Zohar Paleiov, Michael M. Meijler, Tineke Lenstra, Amir Aharoni

Research output: Contribution to journalArticlepeer-review

Abstract

The coexistence of DNA replication and transcription during S-phase requires their tight coordination to prevent harmful conflicts. While extensive research revealed important mechanisms for minimizing these conflicts and their consequences, little is known regarding how the replication and transcription machinery are coordinated in real-time. Here, we developed a live-cell imaging approach for the real-time monitoring of replisome progression and transcription dynamics during a transcription-replication encounter. We found a wave of partial transcriptional repression ahead of the moving replication fork, which may contribute to efficient fork progression through the transcribed gene. Real-time detection of conflicts revealed their negative impact on both processes, leading to fork stalling or slowdown as well as lower transcription levels during gene replication, with different trade-offs observed in defined subpopulations of cells. Our real-time measurements of transcription-replication encounters demonstrate how these processes can proceed simultaneously while maintaining genomic stability, and how conflicts can arise when coordination is impaired.

Original languageEnglish
Pages (from-to)2143-2156
Number of pages14
JournalNucleic Acids Research
Volume50
Issue number4
DOIs
StatePublished - 28 Feb 2022

ASJC Scopus subject areas

  • Genetics

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