Department of Biology, Massachusetts Institute of Technology, Cambridge, USA.
Genes Dev. 2011 Jun 15;25(12):1328-43. doi: 10.1101/gad.2038911.
Following DNA damage, cells typically delay cell cycle progression and inhibit cell division until their chromosomes have been repaired. The bacterial checkpoint systems responsible for these DNA damage responses are incompletely understood. Here, we show that Caulobacter crescentus responds to DNA damage by coordinately inducing an SOS regulon and inhibiting the master regulator CtrA. Included in the SOS regulon is sidA (SOS-induced inhibitor of cell division A), a membrane protein of only 29 amino acids that helps to delay cell division following DNA damage, but is dispensable in undamaged cells. SidA is sufficient, when overproduced, to block cell division. However, unlike many other regulators of bacterial cell division, SidA does not directly disrupt the assembly or stability of the cytokinetic ring protein FtsZ, nor does it affect the recruitment of other components of the cell division machinery. Instead, we provide evidence that SidA inhibits division by binding directly to FtsW to prevent the final constriction of the cytokinetic ring.
在 DNA 损伤后,细胞通常会延迟细胞周期进程并抑制细胞分裂,直到其染色体被修复。负责这些 DNA 损伤反应的细菌检查点系统尚未完全了解。在这里,我们表明,新月柄杆菌通过协调诱导 SOS 调控子并抑制主调控因子 CtrA 来对 DNA 损伤做出反应。SOS 调控子中包含 sidA(SOS 诱导的细胞分裂抑制剂 A),这是一种仅由 29 个氨基酸组成的膜蛋白,有助于在 DNA 损伤后延迟细胞分裂,但在未受损的细胞中是可有可无的。当过量产生时,SidA 足以阻止细胞分裂。然而,与许多其他细菌细胞分裂调节剂不同,SidA 不会直接破坏细胞分裂蛋白 FtsZ 的组装或稳定性,也不会影响细胞分裂机制的其他成分的招募。相反,我们提供的证据表明,SidA 通过直接结合 FtsW 来抑制分裂,从而防止细胞分裂环的最后收缩。