Dewachter Liselot, Verstraeten Natalie, Jennes Michiel, Verbeelen Tom, Biboy Jacob, Monteyne Daniel, Pérez-Morga David, Verstrepen Kevin J, Vollmer Waldemar, Fauvart Maarten, Michiels Jan
Centre of Microbial and Plant Genetics, KU Leuven - University of LeuvenLeuven, Belgium.
Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle UniversityNewcastle upon Tyne, United Kingdom.
Front Microbiol. 2017 Jun 28;8:1193. doi: 10.3389/fmicb.2017.01193. eCollection 2017.
Cell division is a vital part of the cell cycle that is fundamental to all life. Despite decades of intense investigation, this process is still incompletely understood. Previously, the essential GTPase ObgE, which plays a role in a myriad of basic cellular processes (such as initiation of DNA replication, chromosome segregation, and ribosome assembly), was proposed to act as a cell cycle checkpoint in by licensing chromosome segregation. We here describe the effect of a mutant isoform of ObgE (ObgE) that causes cell death by irreversible arrest of the cell cycle at the stage of cell division. Notably, chromosome segregation is allowed to proceed normally in the presence of ObgE, after which cell division is blocked. Under conditions of rapid growth, ongoing cell cycles are completed before cell cycle arrest by ObgE becomes effective. However, cell division defects caused by ObgE then elicit lysis through formation of membrane blebs at aberrant division sites. Based on our results, and because ObgE was previously implicated in cell cycle regulation, we hypothesize that the mutation in ObgE disrupts the normal role of ObgE in cell division. We discuss how ObgE could reveal more about the intricate role of wild-type ObgE in division and cell cycle control. Moreover, since Obg is widely conserved and essential for viability, also in eukaryotes, our findings might be applicable to other organisms as well.
细胞分裂是细胞周期的一个重要部分，对所有生命来说都是至关重要的。尽管经过了数十年的深入研究，但这个过程仍未被完全理解。此前，在众多基本细胞过程（如DNA复制起始、染色体分离和核糖体组装）中发挥作用的必需GTP酶ObgE，被认为通过许可染色体分离在[具体文献未提及的某机制]中充当细胞周期检查点。我们在此描述了一种ObgE突变体亚型（ObgE）的作用，它通过在细胞分裂阶段使细胞周期不可逆停滞而导致细胞死亡。值得注意的是，在存在ObgE的情况下，染色体分离能够正常进行，之后细胞分裂被阻断。在快速生长的条件下，正在进行的细胞周期会在ObgE导致的细胞周期停滞生效之前完成。然而，由ObgE引起的细胞分裂缺陷随后会通过在异常分裂位点形成膜泡而引发细胞裂解。基于我们的结果，并且由于ObgE之前被认为与细胞周期调控有关，我们推测ObgE中的突变破坏了ObgE在细胞分裂中的正常作用。我们讨论了ObgE如何能揭示更多关于野生型ObgE在分裂和细胞周期控制中的复杂作用。此外，由于Obg广泛保守且对生存力至关重要，在真核生物中也是如此，我们的发现可能也适用于其他生物体。
