Fig. 6: Working model for the accumulation of post-replicative DNA:RNA hybrids at TRCs and their impact on fork progression.

During head-on transcription replication conflicts, R-loops can form behind the RNAP and are either processed into DNA:RNA hybrids and/or are efficiently bypassed by the replisome. The DNA:RNA hybrid is thereby transferred to the lagging strand behind the replisome (see Extended Data Figure 8a for potential mechanisms). Under physiological conditions, this hybrid is rapidly resolved, allowing unperturbed fork progression. In case of excessive accumulation (that is transcriptional burst) or impaired removal (that is limited RNase H activity), DNA:RNA hybrids may be still efficiently bypassed, but their accumulation behind the fork would result in delayed fork progression and frequent fork reversal (see Extended Data Fig. 8b for potential mechanisms). Upon stress resolution, the reversed fork can be restarted to complete DNA replication.