Chodavarapu S, Kaguni J M
Michigan State University, East Lansing, MI, United States.
Michigan State University, East Lansing, MI, United States.
Enzymes. 2016;39:1-30. doi: 10.1016/bs.enz.2016.03.001. Epub 2016 Apr 20.
The initiation of chromosomal DNA replication starts at a replication origin, which in bacteria is a discrete locus that contains DNA sequence motifs recognized by an initiator protein whose role is to assemble the replication fork machinery at this site. In bacteria with a single chromosome, DnaA is the initiator and is highly conserved in all bacteria. As an adenine nucleotide binding protein, DnaA bound to ATP is active in the assembly of a DnaA oligomer onto these sites. Other proteins modulate DnaA oligomerization via their interaction with the N-terminal region of DnaA. Following the DnaA-dependent unwinding of an AT-rich region within the replication origin, DnaA then mediates the binding of DnaB, the replicative DNA helicase, in a complex with DnaC to form an intermediate named the prepriming complex. In the formation of this intermediate, the helicase is loaded onto the unwound region within the replication origin. As DnaC bound to DnaB inhibits its activity as a DNA helicase, DnaC must dissociate to activate DnaB. Apparently, the interaction of DnaB with primase (DnaG) and primer formation leads to the release of DnaC from DnaB, which is coordinated with or followed by translocation of DnaB to the junction of the replication fork. There, DnaB is able to coordinate its activity as a DNA helicase with the cellular replicase, DNA polymerase III holoenzyme, which uses the primers made by primase for leading strand DNA synthesis.
染色体DNA复制的起始始于一个复制起点,在细菌中,它是一个离散的位点,包含被起始蛋白识别的DNA序列基序,起始蛋白的作用是在该位点组装复制叉机器。在具有单条染色体的细菌中,DnaA是起始蛋白,在所有细菌中高度保守。作为一种腺嘌呤核苷酸结合蛋白,与ATP结合的DnaA在将DnaA寡聚体组装到这些位点上时具有活性。其他蛋白质通过与DnaA的N端区域相互作用来调节DnaA寡聚化。在复制起点内富含AT的区域发生依赖于DnaA的解旋后,DnaA随后介导复制性DNA解旋酶DnaB与DnaC形成复合物并结合,形成一个名为预引发复合物的中间体。在这个中间体的形成过程中,解旋酶被加载到复制起点内解旋的区域。由于与DnaB结合的DnaC会抑制其作为DNA解旋酶的活性,DnaC必须解离以激活DnaB。显然,DnaB与引发酶(DnaG)的相互作用以及引物的形成会导致DnaC从DnaB上释放,这与DnaB向复制叉连接处的移位同时发生或紧随其后。在那里,DnaB能够将其作为DNA解旋酶的活性与细胞复制酶DNA聚合酶III全酶协调起来,DNA聚合酶III全酶利用引发酶合成的引物进行前导链DNA合成。