SEGREGATION OF BACTERIAL CHROMOSOMES TO DAUGHTER CELLS

细菌中的染色体分离不是通过类似于有丝分裂的机制进行的。相反，这一过程似乎类似于真核细胞中姐妹染色单体的形成；这是一种在任何生物体中都很难理解的机制。我们的研究，以及其他实验室的研究，正开始提供大肠杆菌这一过程的详细图像。其本质是细胞复制机制被束缚在细胞中心，DNA在复制过程中通过它。新复制的DNA被从复制叉引导到每个细胞极点。在那里，DNA被重新折叠并凝聚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，我们通过与半甲基化DNA结合的能力发现了SeqA蛋白，它似乎参与了新合成的DNA从复制叉向细胞极点有序方向的转移。从分叉中出现的DNA具有半甲基化的GATC序列。它们以一种高度合作的方式结合SeqA，产生一束结合蛋白，跟踪分叉。这些束，通过与细胞膜相互作用，似乎引导DNA，使两条新的染色体可以形成独立的团块。其次，我们发现MukB、MukE和MukF蛋白形成真核生物凝缩蛋白的类似物。它们的作用是重新折叠并将新复制的DNA凝聚成靠近细胞两极的新生染色体。这个动作既可以组织染色体，又可以吸收新复制的DNA，以促进其分离。

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.