Head-on replication–transcription conflict is especially bitter in bacterial chromosomes, explaining why actively transcribed genes are always co-oriented with replication. The mechanism of this conflict remains unclear, besides the anticipated accumulation of positive supercoils between head-on-conflicting polymerases. Unexpectedly, experiments in bacterial and human cells reveal that head-on replication–transcription conflict induces R-loops, indicating hypernegative supercoiling [(−)sc] in the region – precisely the opposite of that assumed. Further, as a result of these R-loops, both replication and transcription in the affected region permanently stall, so the failure of R-loop removal in RNase H-deficient bacteria becomes lethal. How hyper(−)sc emerges in the middle of a positively supercoiled chromosomal domain is a mystery that requires rethinking of topoisomerase action around polymerases.

正面复制与转录的冲突在细菌染色体中尤其痛苦，这解释了为什么主动转录的基因总是与复制共同定位。除了预期的正面冲突的聚合酶之间阳性超螺旋的积累之外，这种冲突的机制仍然不清楚。出乎意料的是，在细菌和人类细胞中进行的实验表明，正面复制-转录冲突会诱导R环，表明该区域超负超螺旋[（-）sc] –与假设的恰好相反。此外，由于这些R-环，在受影响区域的复制和转录都永久停止，因此在RNase H缺陷型细菌中去除R-环的失败变得致命。