Department of Biology, University of York, York, Yorkshire, UK,
Adv Exp Med Biol. 2013;767:97-121. doi: 10.1007/978-1-4614-5037-5_5.
Helicases are fundamental components of all replication complexes since unwinding of the double-stranded template to generate single-stranded DNA is essential to direct DNA synthesis by polymerases. However, helicases are also required in many other steps of DNA replication. Replicative helicases not only unwind the template DNA but also play key roles in regulating priming of DNA synthesis and coordination of leading and lagging strand DNA polymerases. Accessory helicases also aid replicative helicases in unwinding of the template strands in the presence of proteins bound to the DNA, minimising the risks posed by nucleoprotein complexes to continued fork movement. Helicases also play critical roles in Okazaki fragment processing in eukaryotes and may also be needed to minimise topological problems when replication forks converge. Thus fork movement, coordination of DNA synthesis, lagging strand maturation and termination of replication all depend on helicases. Moreover, if disaster strikes and a replication fork breaks down then reloading of the replication machinery is effected by helicases, at least in bacteria. This chapter describes how helicases function in these multiple steps at the fork and how DNA unwinding is coordinated with other catalytic processes to ensure efficient, high fidelity duplication of the genetic material in all organisms.
解旋酶是所有复制复合物的基本组成部分,因为双链模板的解旋对于聚合酶直接进行 DNA 合成至关重要。然而,解旋酶在 DNA 复制的许多其他步骤中也是必需的。复制解旋酶不仅解开模板 DNA,而且在调节 DNA 合成的引物起始和领头链和滞后链 DNA 聚合酶的协调方面发挥关键作用。辅助解旋酶还帮助复制解旋酶在与 DNA 结合的蛋白质存在的情况下解开模板链,最大限度地减少核蛋白复合物对持续叉移动的风险。解旋酶在真核生物中也在冈崎片段加工中发挥关键作用,并且在复制叉汇聚时可能也需要最小化拓扑问题。因此,叉移动、DNA 合成的协调、滞后链成熟和复制的终止都依赖于解旋酶。此外,如果发生灾难,复制叉崩溃,那么解旋酶至少在细菌中会重新加载复制机制。本章描述了解旋酶如何在叉处的这些多个步骤中发挥作用,以及 DNA 解旋如何与其他催化过程协调,以确保所有生物体中遗传物质的高效、高保真复制。