The coordinated action of DNA polymerases and DNA helicases is essential at genomic sites that are hard to replicate. Among these are sites that harbour G-quadruplex DNA structures (G4). G4s are stable alternative DNA structures, which have been implicated to be involved in important cellular processes like the regulation of gene expression or telomere maintenance. G4 structures were shown to hinder replication fork progression and cause genomic deletions, mutations and recombination events. Many helicases unwind G4 structures and preserve genome stability, but a detailed understanding of G4 replication and the re-start of stalled replication forks around formed G4 structures is not clear, yet. In our recent study, we identified that Mgs1 preferentially binds to G4 DNA structures in vitro and is associated with putative G4-forming chromosomal regions in vivo. Mgs1 binding to G4 motifs in vivo is partially dependent on the helicase Pif1. Pif1 is the major G4-unwinding helicase in S. cerevisiae. In the absence of Mgs1, we determined elevated gross chromosomal rearrangement (GCR) rates in yeast, similar to Pif1 deletion. Here, we highlight the recent findings and set these into context with a new mechanistic model. We propose that Mgs1's functions support DNA replication at G4-forming regions.

DNA 聚合酶和 DNA 解旋酶的协同作用对于难以复制的基因组位点至关重要。其中包括含有 G-四链体 DNA 结构 (G4) 的位点。G4s 是稳定的替代 DNA 结构，它被认为参与了重要的细胞过程，如基因表达的调节或端粒维持。G4 结构被证明会阻碍复制叉进展并导致基因组缺失、突变和重组事件。许多解旋酶解开 G4 结构并保持基因组稳定性，但对 G4 复制和在形成的 G4 结构周围停滞的复制叉的重新启动的详细了解尚不清楚。在我们最近的研究中，我们发现 Mgs1 在体外优先结合 G4 DNA 结构，并与体内假定的 G4 形成染色体区域相关。Mgs1 在体内与 G4 基序的结合部分依赖于解旋酶 Pif1。Pif1 是主要的 G4 解旋酶酿酒酵母。在没有 Mgs1 的情况下，我们确定了酵母中总染色体重排 (GCR) 率升高，类似于 Pif1 缺失。在这里，我们重点介绍了最近的发现，并将这些发现与新的机械模型结合起来。我们建议 Mgs1 的功能支持 G4 形成区域的 DNA 复制。