Transcription-replication conflicts (TRCs) represent a potential source of endogenous replication stress (RS) and genomic instability in eukaryotic cells but the mechanisms that underlie this instability remain poorly understood. Part of the problem could come from non-B DNA structures called R-loops, which are formed of a RNA:DNA hybrid and a displaced ssDNA loop. In this review, we discuss different scenarios in which R-loops directly or indirectly interfere with DNA replication. We also present other types of TRCs that may not depend on R-loops to impede fork progression. Finally, we discuss alternative models in which toxic RNA:DNA hybrids form at stalled forks as a consequence - but not a cause - of replication stress and interfere with replication resumption.

转录-复制冲突 (TRC) 代表了真核细胞中内源性复制应激 (RS) 和基因组不稳定性的潜在来源，但这种不稳定性背后的机制仍然知之甚少。部分问题可能来自称为 R 环的非 B DNA 结构，它由 RNA:DNA 杂合体和置换的 ssDNA 环形成。在这篇综述中，我们讨论了 R 环直接或间接干扰 DNA 复制的不同情况。我们还介绍了其他类型的 TRC，它们可能不依赖于 R-loop 来阻碍分叉的进展。最后，我们讨论了替代模型，其中有毒 RNA：DNA 杂合体在停滞的叉处形成，作为复制压力的结果 - 但不是原因 - 并干扰复制恢复。