SEGREGATION OF BACTERIAL CHROMOSOMES TO DAUGHTER CELLS

细菌染色体分离到子细胞

• 批准号: 6419951
• 负责人: STUART AUSTIN
• 金额: --
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6419951
• 关键词: DNA binding protein; DNA replication; Escherichia coli; bacterial DNA; bacterial genetics; bacterial proteins

Chromosome segregation in bacteria does not proceed via a mechanism akin to mitosis. Rather, the process appears to resemble sister chromatid formation in eucaryotic cells; a mechanism that is poorly understood in any organism. Our studies, along with those of other laboratories, are starting to provide a detailed picture of the process in Escherichia coli. The essence of this is that the cellular replication machinery is tethered at the cell center, and the DNA passes through it during replication. The newly replicated DNA is directed away from the replication forks toward each cell pole. There, the DNA is refolded and condensed into two separate chromosome masses. We have made progress in elucidating two key activities in the process. First, the SeqA protein, which we discovered by its ability to bind to hemimethylated DNA, appears to be involved in the orderly direction of the newly synthesized DNA away from the replication forks and toward the cell poles. DNA emerging from the forks is uniquely marked by having hemimethylated GATC sequences. These bind SeqA in a highly cooperative fashion, resulting in a tract of bound protein which tracks the forks. These tracts, by interacting with the cell membrane, appear to direct the DNA such that two new chromosomes can form as separate masses. Second, we have found that the MukB, MukE and MukF proteins form an analog of eucaryotic condensins. They act to re-fold and condense the newly replicated DNA into nascent chromosomes in areas of the cell adjacent to the cell poles. This action serves both to organize the chromosomes and to reel in the newly replicated DNA to facilitate its segregation.

细菌中的染色体分离不通过类似于有丝分裂的机制进行。 相反，这一过程似乎类似于真核细胞中的姐妹染色单体形成;这是一种在任何生物中都知之甚少的机制。 我们的研究，沿着其他实验室的研究，开始提供大肠杆菌中这一过程的详细情况。 其本质是细胞复制机制被束缚在细胞中心，DNA在复制过程中穿过它。 新复制的DNA被引导离开复制叉朝向每个细胞极。 在那里，DNA被重折叠并浓缩成两个独立的染色体团。我们在阐明这一进程中的两项关键活动方面取得了进展。 首先，我们发现SeqA蛋白能够与半甲基化DNA结合，它似乎参与了新合成的DNA从复制叉向细胞两极的有序方向移动。 从分叉出现的DNA通过具有半甲基化的GATC序列而被独特地标记。 它们以高度合作的方式与SeqA结合，产生一段跟踪分叉的结合蛋白。 这些束通过与细胞膜相互作用，似乎可以引导DNA，使得两个新的染色体可以形成单独的团块。 其次，我们发现MukB、MukE和MukF蛋白形成真核凝聚素的类似物。 它们的作用是将新复制的DNA重新折叠并浓缩成细胞两极附近区域的新生染色体。 这一作用既可以组织染色体，也可以卷起新复制的DNA以促进其分离。