DNA helicases and their roles in cancer

Dhar, Srijita; Datta, Asoke G.; Brosh, Robert M.

doi:10.1016/j.dnarep.2020.102994

Cited by 24 publications

(21 citation statements)

References 411 publications

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“…Due to the ubiquity of G4 structures in promoters, promoter-enhancement regions, and oncogenes, much of helicase study focuses on how these enzymes unwind DNA and RNA and their impact on cancer tumorigenesis [ 3 ]. Helicase enzyme levels are increased in several cancers and mutations or deletion of helicase genes often lead to cancer ( Figure 2 ) [ 23 ].…”

Section: Dhx36 In Cancermentioning

confidence: 99%

G-Quadruplexes and the DNA/RNA helicase DHX36 in health, disease, and aging

Antcliff

McCullough

Tsvetkov

2021

Aging

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G-Quadruplex (G4) DNA (G4 DNA) and RNA (G4 RNA) are secondary nucleic acid structures that have multiple roles in vital cellular processes. G4 DNA- and RNA-binding proteins and unwinding helicases associate with and regulate G4s during virtually all processes that involve DNA and RNA. DEAH-Box helicase 36 (DHX36), a member of the large DExD/H box helicase family, enzymatically unwinds both G4 DNA and G4 RNA. By exerting its G4 helicase function, DHX36 regulates transcription, genomic stability, telomere maintenance, translation and RNA metabolism. This review will provide an overview of G4s and DHX36, including DHX36’s potential role in neuronal development and neurodegeneration. We conclude with a discussion of the possible functions of G4s and DHX36 in the aging brain.

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Section: Dhx36 In Cancermentioning

confidence: 99%

G-Quadruplexes and the DNA/RNA helicase DHX36 in health, disease, and aging

Antcliff

McCullough

Tsvetkov

2021

Aging

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“…However, future studies are required to verify whether such conditions result from either polymerase I deficiency or abnormal G4 metabolism or both. Strikingly, most of these syndromes have an increased propensity to develop various cancers, a characteristic of many helicase disorders [Dhar et al, 2020].…”

Section: Plausible Involvement Of G4 In Disease Pathogenesis Arising From Defective Rdna Metabolismmentioning

confidence: 99%

G-Quadruplex Assembly by Ribosomal DNA: Emerging Roles in Disease Pathogenesis and Cancer Biology

Datta

Pollock

Kormuth

et al. 2021

Cytogenet Genome Res

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Unique repetitive elements of the eukaryotic genome can be problematic for cellular DNA replication and transcription and pose a source of genomic instability. Human ribosomal DNA (rDNA) exists as repeating units clustered together on several chromosomes. Understanding the molecular mechanisms whereby rDNA interferes with normal genome homeostasis is the subject of this review. We discuss the instability of rDNA as a driver of senescence and the important roles of helicases to suppress its deleterious effects. The propensity of rDNA that is rich in guanine bases to form G-quadruplexes (G4) is discussed and evaluated in disease pathogenesis. Targeting G4 in the ribosomes and other chromosomal loci may represent a useful synthetic lethal approach to combating cancer.

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“…The forgoing account clearly illustrates that loss or gain of expression of RecQ helicases is linked with cancer susceptibility. Therefore, several studies have suggested the possibility of targeting RecQ helicases for cancer therapy [Sharma et al, 2005;Gupta and Brosh, 2007;Xi, 2007;Arai et al, 2011;Futami and Furuichi, 2014;Moles et al, 2016;Dhar et al, 2020]. Since RecQ helicases play important roles in DNA repair, targeting them may constitute an innovative strategy for sensitizing the cancer cells to radioand chemotherapeutic agents [Jain et al, 2020].…”

Section: Figmentioning

confidence: 99%

Human RecQL4 as a Novel Molecular Target for Cancer Therapy

Balajee¹

2021

Cytogenet Genome Res

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Human RecQ helicases play diverse roles in the maintenance of genomic stability. Inactivating mutations in 3 of the 5 human RecQ helicases are responsible for the pathogenesis of Werner syndrome (WS), Bloom syndrome (BS), Rothmund-Thomson syndrome (RTS), RAPADILINO, and Baller-Gerold syndrome (BGS). WS, BS, and RTS patients are at increased risk for developing many age-associated diseases including cancer. Mutations in RecQL1 and RecQL5 have not yet been associated with any human diseases so far. In terms of disease outcome, RecQL4 deserves special attention because mutations in RecQL4 result in 3 autosomal recessive syndromes (RTS type II, RAPADILINO, and BGS). RecQL4, like other human RecQ helicases, has been demonstrated to play a crucial role in the maintenance of genomic stability through participation in diverse DNA metabolic activities. Increased incidence of osteosarcoma in RecQL4-mutated RTS patients and elevated expression of RecQL4 in sporadic cancers including osteosarcoma suggest that loss or gain of RecQL4 expression is linked with cancer susceptibility. In this review, current and future perspectives are discussed on the potential use of RecQL4 as a novel cancer therapeutic target.

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DNA helicases and their roles in cancer

Cited by 24 publications

References 411 publications

G-Quadruplexes and the DNA/RNA helicase DHX36 in health, disease, and aging

G-Quadruplexes and the DNA/RNA helicase DHX36 in health, disease, and aging

G-Quadruplex Assembly by Ribosomal DNA: Emerging Roles in Disease Pathogenesis and Cancer Biology

Human RecQL4 as a Novel Molecular Target for Cancer Therapy

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