Chromosome segregation drives division site selection in Streptococcus pneumoniae
Chromosome segregation drives division site selection in Streptococcus pneumoniae
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DOI：
10.1073/pnas.1620608114
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发表时间：
2016-11
期刊：
影响因子：
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通讯作者：
Renske van Raaphorst;M. Kjos;J. Veening
中科院分区：
文献类型：
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作者：
Renske van Raaphorst;M. Kjos;J. Veening
精确的细胞分裂对所有细胞生命都至关重要。在每年导致超过100万人死亡的肺炎球菌中，MapZ蛋白最近被确定为分裂位点的标记物。通过开发一套工具，包括染色体标记系统和基于CRISPR/ cas9的染色体分离扰动，我们详细绘制了肺炎球菌的细胞周期。我们表明MapZ不参与分区选址，但对于设置正确的分区平面角度很重要。重要的是，我们证明了肺炎球菌具有独特的染色体组织，染色体起源到未来细胞分裂位点的及时复制和分离是细胞分裂蛋白正确定位的关键决定因素。微管蛋白样蛋白FtsZ的准确时空定位是细菌细胞正常分裂的关键。肺炎链球菌（肺炎球菌）是一种椭圆形，对称分裂的机会性人类病原体，缺乏分裂部位控制的规范系统（类核闭塞和min系统）。最近，早期分裂蛋白MapZ被确定并参与肺炎球菌分裂位点的选择。我们证明了MapZ对于正确划分平面的选择是重要的；因此，问题仍然是什么驱动肺炎球菌分裂位点的选择。通过绘制细胞周期的详细图，我们发现在复制后，两条染色体的起源区域都直接定位到未来的细胞分裂位点，在FtsZ之前。有趣的是，z环的形成与DNA复制的开始是一致的。通过突变凝缩蛋白SMC、通过CRISPR/ cas9介导的染色体切割、或者通过毒化DNA decatenation来扰乱染色体纵向组织，导致MapZ和FtsZ定位的错误时间和随后的细胞伸长。总之，我们证明了在肺炎球菌中DNA复制、染色体分离和分裂位点选择之间的密切关系，提供了一种简单的方法来确保大小相等的子细胞。
Significance Precise cell division is crucial for all cellular life. In the pneumococcus, which kills more than a million people annually, the protein MapZ was recently identified as a marker for the division site. By developing a suite of tools, including a chromosome labeling system and CRISPR/Cas9-based perturbation of chromosome segregation, we mapped the pneumococcal cell cycle in detail. We show that MapZ is not involved in division site selection but is important for setting the correct angle of the division plane. Importantly, we demonstrate that the pneumococcus has a unique chromosomal organization and that timely replication and segregation of the chromosomal origin to the future cell division site is a key determinant for correct positioning of cell division proteins. Accurate spatial and temporal positioning of the tubulin-like protein FtsZ is key for proper bacterial cell division. Streptococcus pneumoniae (pneumococcus) is an oval-shaped, symmetrically dividing opportunistic human pathogen lacking the canonical systems for division site control (nucleoid occlusion and the Min-system). Recently, the early division protein MapZ was identified and implicated in pneumococcal division site selection. We show that MapZ is important for proper division plane selection; thus, the question remains as to what drives pneumococcal division site selection. By mapping the cell cycle in detail, we show that directly after replication both chromosomal origin regions localize to the future cell division sites, before FtsZ. Interestingly, Z-ring formation occurs coincidently with initiation of DNA replication. Perturbing the longitudinal chromosomal organization by mutating the condensin SMC, by CRISPR/Cas9-mediated chromosome cutting, or by poisoning DNA decatenation resulted in mistiming of MapZ and FtsZ positioning and subsequent cell elongation. Together, we demonstrate an intimate relationship between DNA replication, chromosome segregation, and division site selection in the pneumococcus, providing a simple way to ensure equally sized daughter cells.