Transcription can wait. Analysis of the role of the DNA/RNA helicase Sen1 at replication forks
DNA replication occurs only once per cell cycle and must fully and faithfully duplicate the chromosomes. Failures in this process can lead to loss of heterozygosity, double-stranded DNA breaks, chromosome rearrangements, and, in higher eukaryotes, cell transformation. Eukaryotic cells have evolved a complex and robust machine (the replisome) that physically and functionally couples DNA unwinding with DNA synthesis. Nevertheless, many obstacles can interfere with the timely duplication of the DNA. RNA transcription bubbles and the resulting DNA/RNA hybrids (R-loops) can stall forks and must be removed for DNA synthesis to proceed. How the replisome overcomes this barrier, it’s however still poorly understood. Our work shows how the replisome binds the DNA/RNA helicase and transcription termination factor Sen1. We map the interaction sites and generate a mutant that fail to bind to the replisome while still proficient in transcription termination. This allows us to explore the importance of Sen1 at forks and its role in genome stability.