The guanine-rich stretch of single-stranded DNA (ssDNA) forms a G-quadruplex (G4) in a fraction of genic and intergenic chromosomal regions. The probability of G4 formation increases during events causing ssDNA generation, such as transcription and replication. In turn, G4 abrogates these events, leading to DNA damage. DHX36 unwinds G4-DNA in vitro and in human cells. However, its spatial correlation with G4-DNA in vivo and its role in genome maintenance remain unclear. Here, we demonstrate a connection between DHX36 and G4-DNA and its implications for genomic integrity. The nuclear localization of DHX36 overlapped with that of G4-DNA, RNA polymerase II, and a splicing-related factor. Depletion of DHX36 resulted in accumulated DNA damage, slower cell growth, and enhanced cell growth inhibition upon treatment with a G4-stabilizing compound; DHX36 expression reversed these defects. In contrast, the reversal upon expression of DHX36 mutants that could not bind G4 was imperfect. Thus, DHX36 may suppress DNA damage by promoting the clearance of G4-DNA for cell growth and survival. Our findings deepen the understanding of G4 resolution in the maintenance of genomic integrity.

中文翻译：

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DHX36 通过解开 G 四链体来维持基因组完整性

富含鸟嘌呤的单链 DNA (ssDNA) 在基因和基因间染色体区域的一部分中形成 G 四链体 (G4)。在引起 ssDNA 生成的事件（例如转录和复制）期间，G4 形成的可能性会增加。反过来，G4 会废除这些事件，导致 DNA 损伤。DHX36 在体外和人类细胞中解开 G4-DNA。然而，其与体内 G4-DNA 的空间相关性及其在基因组维护中的作用仍不清楚。在这里，我们展示了 DHX36 和 G4-DNA 之间的联系及其对基因组完整性的影响。DHX36 的核定位与 G4-DNA、RNA 聚合酶 II 和剪接相关因子的核定位重叠。DHX36 的耗尽会导致 DNA 损伤累积、细胞生长减慢，并在用 G4 稳定化合物处理后增强细胞生长抑制作用；DHX36 表达逆转了这些缺陷。相反，不能结合 G4 的 DHX36 突变体表达后的逆转是不完美的。因此，DHX36 可能通过促进细胞生长和存活的 G4-DNA 清除来抑制 DNA 损伤。我们的研究结果加深了对 G4 分辨率在维持基因组完整性方面的理解。