Figure 7. Integrative view and model showing how the lack of DNA Damage Checkpoint and Post‐replicative Repair factors can affect DNA–RNA hybrid homeostasis.

1. DNA–RNA hybrids, DNA damage, and fork stalling in 9‐1‐1/ATR/CHK1, ATM/CHK2, and PRR‐deficient cells. DNA–RNA hybrids represent the mean ± SEM of all the DRIP data from Fig 2A. ***P < 0.001, *P < 0.05 (paired t‐test). DNA damage represents the mean of medians ± SEM of all the comet tail moment data from Fig 3B. **P < 0.01, *P < 0.05 (paired t‐test). Fork stalling represents the median, 25–75 (boxes) and 10–90 percentiles (whiskers) of all the fork asymmetry data from Fig 5B. ***P < 0.001, **P < 0.01 (Mann–Whitney U‐test). Black stars denote significant increases, whereas red stars denote significant decreases.
2. A model to show that spontaneous DNA–RNA hybrids impairing replication fork progression would require the 9‐1‐1/ATR/CHK1 for dissolution. Additionally, unrepaired DSBs (accumulated as a consequence of ATM/CHK2 depletion) and post‐replicative ssDNA gaps (present in PRR‐defective cells) could favor DNA–RNA hybrid accumulation without stalling replication forks.