Abstract
DEAD-box RNA helicases are important regulators of RNA metabolism and have been implicated in the development of cancer. Interestingly, these helicases constitute a major recurring family of RNA-binding proteins important for protecting the genome. Current studies have provided insight into the connection between genomic stability and several DEAD-box RNA helicase family proteins including DDX1, DDX3X, DDX5, DDX19, DDX21, DDX39B, and DDX41. For each helicase, we have reviewed evidence supporting their role in protecting the genome and their suggested mechanisms. Such helicases regulate the expression of factors promoting genomic stability, prevent DNA damage, and can participate directly in the response and repair of DNA damage. Finally, we summarized the pathological and therapeutic relationship between DEAD-box RNA helicases and cancer with respect to their novel role in genome stability.
Highlights
RNA helicases of the DEAD-box family belong to the helicase superfamily 2 (SF2), one of the largest families of RNA helicases present in eukaryotes, archaea and bacteria [1].DEAD-box RNA (DDX) helicases are characterized by the presence of a specific amino acid motif, Asp-Glu-Ala-Asp (DEAD)
Helicases tioned are listed. (A) DDX RNA helicases promote the expression of genes important for genome stability (represented in mentioned are listed. (A) DDX RNA helicases promote the expression of genes important for genome stability in addition to regulating their expression via microRNAs. (B) DDX RNA helicases are directly involved in the dotted lines) in addition to regulating their expression via microRNAs. (B) DDX RNA helicases are directly involved with the DDR either via DNA repair or the p53 DNA damage signaling axis, typically associated with the RNA metabolism with theof either via DNA
Further investigation of these helicases via screens, high-throughput assays and multiomics approaches in the context of genome stability could identify potential new DDX helicases as biomarkers for diagnosis and prognosis, or as pharmacological drug targets for cancer. One such TCGA screen of candidate genes in colorectal cancer identified that loss of DDX56 reduced intron retention and tumor suppressor WEE1 expression, which functions as a G2-M DNA damage checkpoint, postulating that DDX56 could serve as a potential prognostic biomarker of colorectal cancer [85]
Summary
RNA helicases of the DEAD-box family belong to the helicase superfamily 2 (SF2), one of the largest families of RNA helicases present in eukaryotes, archaea and bacteria [1]. We will summarize the evidence supporting this novel function of DDX helicases, focusing on seven members whose roles in promoting genome integrity have been highlighted in recent studies. Genes 2021, 12, 1471 genome integrity have been highlighted in recent studies Helicases described in this review with a role in promoting genome integrity are highlighted in generated with Phylogeny.fr.
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