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Mgs1 protein supports genome stability via recognition of G-quadruplex DNA structures
The FASEB Journal ( IF 4.8 ) Pub Date : 2020-08-04 , DOI: 10.1096/fj.202000886r
Theresa Zacheja 1 , Agnes Toth 2, 3 , Gabor M Harami 4 , Qianlu Yang 5, 6 , Eike Schwindt 1 , Mihály Kovács 4, 7 , Katrin Paeschke 1, 5 , Peter Burkovics 2
Affiliation  

The integrity of the genetic material is crucial for every organism. One intrinsic attack to genome stability is stalling of the replication fork which can result in DNA breakage. Several factors, such as DNA lesions or the formation of stable secondary structures (eg, G‐quadruplexes) can lead to replication fork stalling. G‐quadruplexes (G4s) are well‐characterized stable secondary DNA structures that can form within specific single‐stranded DNA sequence motifs and have been shown to block/pause the replication machinery. In most genomes several helicases have been described to regulate G4 unfolding to preserve genome integrity, however, different experiments raise the hypothesis that processing of G4s during DNA replication is more complex and requires additional, so far unknown, proteins. Here, we show that the Saccharomyces cerevisiae Mgs1 protein robustly binds to G4 structures in vitro and preferentially acts at regions with a strong potential to form G4 structures in vivo. Our results suggest that Mgs1 binds to G4‐forming sites and has a role in the maintenance of genome integrity.

中文翻译:

Mgs1 蛋白通过识别 G-四链体 DNA 结构支持基因组稳定性

遗传物质的完整性对每个生物体都至关重要。对基因组稳定性的一种内在攻击是复制叉的停滞,这可能导致 DNA 断裂。几个因素,例如 DNA 损伤或稳定二级结构的形成(例如,G-四链体)可导致复制叉停滞。G-四链体 (G4s) 是表征良好的稳定二级 DNA 结构,可以在特定的单链 DNA 序列基序中形成,并已被证明可以阻断/暂停复制机制。在大多数基因组中,已经描述了几种解旋酶来调节 G4 展开以保持基因组完整性,但是,不同的实验提出了这样的假设,即 DNA 复制过程中 G4 的加工更复杂,需要额外的、迄今为止未知的蛋白质。这里,我们表明酿酒酵母 Mgs1 蛋白在体外与 G4 结构牢固结合,并优先作用于在体内具有形成 G4 结构的强大潜力的区域。我们的结果表明 Mgs1 与 G4 形成位点结合并在维持基因组完整性方面发挥作用。
更新日期:2020-08-04
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