Figure 7.

Model for DNA-RNA Hybrid Accumulation in sen1 Mutants at Sites of Collision between Replication and Transcription

The ATR checkpoint inhibits gene gating to allow fork progression through topological barriers imposed by RNAPII-transcribed genes. Following gene loop dismantlement, twin-supercoiled domains transiently form, and nascent transcripts may anneal to the negatively supercoiled DNA behind the transcription bubble, leading to DNA-RNA hybrid formation. Sen1 moves with the fork, preventing DNA-RNA hybrid accumulation at those genomic regions at which transcription collides head-on with replication. In the absence of Sen1, DNA-RNA hybrids persist on the lagging strand template. Replication across the nontranscribed strand might be facilitated by the uncoupling of leading- and lagging-strand synthesis.