UV‐induced DNA damage disrupts the coordination between replication initiation, elongation and completion
UV‐induced DNA damage disrupts the coordination between replication initiation, elongation and completion
复制标题
紫外线诱导的 DNA 损伤破坏了复制起始、延伸和完成之间的协调
DOI：
10.1111/gtc.12826
复制
发表时间：
2021
期刊：
影响因子：
2.1
通讯作者：
Courcelle, Justin
中科院分区：
文献类型：
--
作者：
Wendel, Brian M.;Hollingsworth, Suzanne;Courcelle, Charmain T.;Courcelle, Justin
复制开始、延长和完成被紧密协调，以确保所有序列每一代精确复制一次。紫外线诱导的DNA损伤扰乱了复制并延缓了延伸，这可能会破坏这种协调，导致基因组不稳定和细胞死亡。在这里，我们描述了大肠杆菌从紫外线照射中恢复的过程，以确定这些复制过程是如何反应的。我们发现，在这个区域，我们继续发生拷贝数丰富的启动子。在后期，neworiC的启动和在末端汇聚的延迟的伸长叉子的组合似乎对完成反应造成压力或损害，导致染色体这一区域的瞬时过度复制。在恢复伸长受损的突变体中，包括recA、recFanduvrA，基因组退化或保持静止，这表明细胞死亡发生在复制中断后的早期，留下部分复制的基因组。在不能完成复制的突变体中，包括recBC、sbcCD xonA和recG，伸长和起始的恢复导致了一个瓶颈，基因组的无端区被放大和积累，这表明在这些突变体中发生了延迟的细胞死亡，可能是由于细胞分裂时不平衡或未分解的染色体的错误分离所致。
Replication initiation, elongation and completion are tightly coordinated to ensure that all sequences replicate precisely once each generation. UV‐induced DNA damage disrupts replication and delays elongation, which may compromise this coordination leading to genome instability and cell death. Here, we profiled theEscherichia coligenome as it recovers from UV irradiation to determine how these replicational processes respond. We show thatoriCinitiations continue to occur, leading to copy number enrichments in this region. At late times, the combination of neworiCinitiations and delayed elongating forks converging in the terminus appear to stress or impair the completion reaction, leading to a transient over‐replication in this region of the chromosome. In mutants impaired for restoring elongation, includingrecA,recFanduvrA, the genome degrades or remains static, suggesting that cell death occurs early after replication is disrupted, leaving partially duplicated genomes. In mutants impaired for completing replication, includingrecBC,sbcCD xonAandrecG, the recovery of elongation and initiation leads to a bottleneck, where the nonterminus region of the genome is amplified and accumulates, indicating that a delayed cell death occurs in these mutants, likely resulting from mis‐segregation of unbalanced or unresolved chromosomes when cells divide.