Kouzminova Elena A, Cronan Glen E, Kuzminov Andrei
Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States.
Nucleic Acids Res. 2025 Apr 10;53(7). doi: 10.1093/nar/gkaf282.
The rnhAB mutants of Escherichia coli lacking both RNase H enzymes are unexpectedly UV-sensitive, being unable to restore normal levels of post-UV replication. Examining patterns of chromosomal replication in the rnhAB mutants after UV could identify the problem sites. We show that normal rnhA (B) mutant replication initiates at three distinct oriK areas in the origin macrodomain, none of them coinciding with oriC proper, the dominant origin being some 400 kb away. Interestingly, initiation after UV switches to the DnaA-dependent oriK closest to oriC and continues from there until the growth replication pattern is restored, like in the rnhA single mutants. However, in the rnhAB double mutant, post-UV forks initiated at the new origin have difficulty reaching the terminus, with the major stalling sites at the rrn operons. In the rnhAB recBC mutants, additionally deficient in linear DNA degradation/repair, post-UV replication forks cannot traverse the origin-distal ribosomal RNA operons, rrnG and rrnH, showing that restoration of disintegrated replication forks is essential for replication in the rnhAB mutant. In contrast, the rnhAB rpoB* mutant, in which transcription complexes are unstable, is UV-resistant and resumes normal replication even faster than WT cells, indicating that the rnhAB mutants suffer from UV-induced replication-transcription conflicts.
缺乏两种核糖核酸酶H的大肠杆菌rnhAB突变体对紫外线异常敏感,无法恢复紫外线照射后正常的复制水平。检测紫外线照射后rnhAB突变体中的染色体复制模式可以确定问题位点。我们发现,正常的rnhA(B)突变体复制在起始宏观结构域的三个不同的oriK区域开始,它们都不与真正的oriC重合,主要起始点在约400 kb之外。有趣的是,紫外线照射后的起始切换到最接近oriC的依赖DnaA的oriK,并从那里继续,直到恢复生长复制模式,就像在rnhA单突变体中一样。然而,在rnhAB双突变体中,紫外线照射后在新起始点起始的复制叉难以到达终点,主要停滞位点在rrn操纵子处。在rnhAB recBC突变体中,额外缺乏线性DNA降解/修复能力,紫外线照射后的复制叉无法穿过起始点远端的核糖体RNA操纵子rrnG和rrnH,这表明恢复解体的复制叉对rnhAB突变体中的复制至关重要。相比之下,转录复合物不稳定的rnhAB rpoB*突变体对紫外线有抗性,甚至比野生型细胞更快恢复正常复制,这表明rnhAB突变体遭受紫外线诱导的复制-转录冲突。